gebhart/patrepeval huggingface dataset:
Synthesis of ABA Triblock Copolymers via a Tandem Ring-Opening Metathesis Polymerization:  Atom Transfer Radical Polymerization Approach (2000)

The synthesis of poly(styrene)-b-poly(butadiene)-b-poly(styrene) (SBS) and poly(methyl methacrylate)-b-poly(butadiene)-b-poly(methyl methacrylate) (MBM) triblock copolymers with poly(butadiene) (PBD) segments containing 100% 1,4-microstructure is described. Bis(allyl chloride) and bis(2-bromopropionate) terminated telechelic PBD's were synthesized by the ring-opening metathesis polymerization (ROMP) of 1,5-cyclooctadiene in the presence of the corresponding difunctional chain transfer agents. These telechelic PBDs were subsequently used as difunctional macroinitiators for the heterogeneous atom transfer radical polymerization (ATRP) of styrene and methyl methacrylate to form SBS and MBM triblock copolymers. Triblock structure was confirmed by selective PBD degradation. In addition, the tandem ROMP−ATRP approach was successfully extended to a “one-pot” synthesis.
Numerical Recipes in FORTRAN (1988)

Note: Includes bibliographical references and index.- Diskette v 2.04, 3.5'' (720k) for IBM PC, PS/2 and compatibles [DOS] Reference Record created on 2004-09-07, modified on 2016-08-08
Effects of Interferon-Gamma on Bone Remodeling during Experimental Tooth Movement (2007)

IFN-gamma administration may be useful clinically for anchorage control.
Mutation in a “ tesB -Like” Hydroxyacyl-Coenzyme A-Specific Thioesterase Gene Causes Hyperproduction of Extracellular Polyhydroxyalkanoates by Alcanivorax borkumensis SK2 (2006)

A novel mutant of the marine oil-degrading bacterium Alcanivorax borkumensis SK2, containing a mini-Tn5 transposon disrupting a "tesB-like" acyl-coenzyme A (CoA) thioesterase gene, was found to hyperproduce polyhydroxyalkanoates (PHA), resulting in the extracellular deposition of this biotechnologically important polymer when grown on alkanes. The tesB-like gene encodes a distinct novel enzyme activity, which acts exclusively on hydroxylated acyl-CoAs and thus represents a hydroxyacyl-CoA-specific thioesterase. Inactivation of this enzyme results in the rechanneling of CoA-activated hydroxylated fatty acids, the cellular intermediates of alkane degradation, towards PHA production. These findings may open up new avenues for the development of simplified biotechnological processes for the production of PHA as a raw material for the production of bioplastics.
Effect of time of oocyte collection and site of insemination on oocyte transfer in mares1 (2002)

The objective of the study was to compare embryo development rates after transfer of oocytes collected 22 or 33 h after hCG injection into recipients inseminated within the uterus or the oviduct. Oocytes were collected at approximately 22 or 33 h after hCG injections and incubated for approximately 16 or 1.5 h, respectively, before transfer. Intrauterine inseminations using 1 x 10(9) progressively motile sperm were done approximately 12 h before and 2 h after transfer. For intraoviductal inseminations (gamete intrafallopian transfer [GIFT]), semen was centrifuged through a Percoll gradient, and 200,000 progressively motile sperm were transferred with oocytes into the oviduct. Time of oocyte collection (22 or 33 h) after hCG injection did not affect embryo development rates (17/25, 68%, vs 12/23, 52%, respectively; P = 0.40). When results from oocyte collections at 22 and 33 h after hCG were combined, oocyte transfer with intraoviductal vs intrauterine insemination resulted in similar (P = 0.70) embryo development rates (12/22, 55%, and 17/26, 65%, respectively). However, the interaction between time of oocyte collection and site of insemination tended to be significant (P = 0.09), suggesting that GIFT using oocytes collected at 33 h after hCG may not be as effective as using oocytes collected at 22 h after hCG. Because intraoviductal insemination requires a low number of sperm, GIFT could be used in cases of male subfertility, frozen semen, or sexed sperm.
Structural insights into the interaction of IL-33 with its receptors (2013)

Interleukin (IL)-33 is an important member of the IL-1 family that has pleiotropic activities in innate and adaptive immune responses in host defense and disease. It signals through its ligand-binding primary receptor ST2 and IL-1 receptor accessory protein (IL-1RAcP), both of which are members of the IL-1 receptor family. To clarify the interaction of IL-33 with its receptors, we determined the crystal structure of IL-33 in complex with the ectodomain of ST2 at a resolution of 3.27 Å. Coupled with structure-based mutagenesis and binding assay, the structural results define the molecular mechanism by which ST2 specifically recognizes IL-33. Structural comparison with other ligand-receptor complexes in the IL-1 family indicates that surface-charge complementarity is critical in determining ligand-binding specificity of IL-1 primary receptors. Combined crystallography and small-angle X-ray-scattering studies reveal that ST2 possesses hinge flexibility between the D3 domain and D1D2 module, whereas IL-1RAcP exhibits a rigid conformation in the unbound state in solution. The molecular flexibility of ST2 provides structural insights into domain-level conformational change of IL-1 primary receptors upon ligand binding, and the rigidity of IL-1RAcP explains its inability to bind ligands directly. The solution architecture of IL-33-ST2-IL-1RAcP complex from small-angle X-ray-scattering analysis resembles IL-1β-IL-1RII-IL-1RAcP and IL-1β-IL-1RI-IL-1RAcP crystal structures. The collective results confer IL-33 structure-function relationships, supporting and extending a general model for ligand-receptor assembly and activation in the IL-1 family.
The Role of Catalytic Cleft and Exosite Residues of Factor VIIa for Complex Formation with Tissue Factor Pathway Inhibitor (2001)

The extrinsic coagulation pathway is initiated by the binding of plasma factor VIIa (VIIa) to the cell surface receptor tissue factor (TF). Formation of the TF-VIIa complex results in allosteric activation of VIIa as well as the creation of an extended macromolecular substrate binding exosite that greatly enhances proteolytic activation of substrate factor X. The catalytic function of the TF-VIIa complex is regulated by a specific Kunitz-type inhibitor, tissue factor pathway inhibitor (TFPI). TFPI inhibition of the TF-VIIa complex was enhanced by the presence of Xa. This study investigates the relative contribution of catalytic cleft and exosite residues in VIIa for inhibitory complex formation with TFPI. VIIa protease domain residues Q176, T239 and E296 are involved in the formation of stable inhibitor complex with free TFPI. Kinetic analysis further demonstrated a predominant role of the S2' subsite residue Q176 for the initial complex formation with TFPI. In contrast, no significant reductions in inhibition by TFPI-Xa were found for each of the mutants in complex with phospholipid reconstituted TF. However, reduced rates of inhibition of the VIIa Gla-domain (R36) and Q176 mutant by TFPI-Xa were evident when TF was solubilized by detergent micelles. These data demonstrate docking of the TFPI-Xa complex with the macromolecular substrate exosite and the catalytic cleft, in particular the S2' subsite. The masking of the mutational effect by the presence of phospholipid shows a critical importance of Xa Gla-domain interactions in stabilizing the quaternary TF-VIIa-Xa-TFPI complex.
Pulmonary Vasodilatory Action of Testosterone: Evidence of a Calcium Antagonistic Action (2002)

Recent evidence supports a beneficial effect of testosterone on the cardiovascular system. Testosterone acts as a coronary vasodilator and reduces myocardial ischemia in men with coronary heart disease. The aim of the current study was to determine whether testosterone has a similar vasodilatory action in the pulmonary circulation and to characterize the underlying mechanism of action. The vasodilatory action of testosterone was studied in pulmonary arteries (n = 132, mean internal diameter = 344 +/- 8 microm) isolated from male rats (n = 48, mass = 396 +/- 7 g) mounted in a small vessel wire myograph and loaded to a tension equivalent to 17.5 mm Hg. Micromolar concentrations of testosterone induced dilatation in pulmonary arteries preconstricted with prostaglandin F2alpha (100 microM) within seconds of application. Dilatation to testosterone was similar in vessels treated with N-gamma-nitro-l-arginine methyl ester (l-NAME) (10 microM) or vehicle (5 microl distilled water), -38.2 +/- 2.9%, and -38.1 +/- 3.4%, respectively, and in vessels treated with indomethacin (10 microM), flutamide (10 microM), or vehicle (5 microl ethanol), -35.5 +/- 2.8%, -43.2 +/- 3.6%, and -35.7 +/- 4.6%, respectively (all p > 0.05). Maximal dilatation to testosterone occurred following preconstriction with agents that activated voltage-gated calcium channels such as prostaglandin F2alpha (-34.6 +/- 5.0%), BAY K8644 (-32.9 +/- 8.7), or potassium chloride (-26.7 +/- 1.5%), compared with calcium-independent protein kinase C activation by phorbol dibutyrate (-14.7 +/- 1.6%) or capacitative calcium entry via thapsigargin (-5.1 +/- 0.9%). This study demonstrates that testosterone induces pulmonary dilatation via a mechanism that is independent of the classic androgen receptor and also of the release of nitric oxide or dilator prostaglandins. The data support a calcium antagonistic action for testosterone in the pulmonary circulation, primarily against voltage-gated calcium channels.
Targeted DNA recombination in vivo using an adenovirus carrying the cre recombinase gene. (1996)

Conditional gene expression and gene deletion are important experimental approaches for examining the functions of particular gene products in development and disease. The cre-loxP system from bacteriophage P1 has been used in transgenic animals to induce site-specific DNA recombination leading to gene activation or deletion. To regulate the recombination in a spatiotemporally controlled manner, we constructed a recombinant adenoviral vector, Adv/cre, that contained the cre recombinase gene under regulation of the herpes simplex virus thymidine kinase promoter. The efficacy and target specificity of this vector in mediating loxP-dependent recombination were analyzed in mice that had been genetically engineered to contain loxP sites in their genome. After intravenous injection of the Adv/cre vector into adult animals, the liver and spleen showed the highest infectivity of the adenovirus as well as the highest levels of recombination, whereas other tissues such as kidney, lung, and heart had lower levels of infection and recombination. Only trace levels of recombination were detected in the brain. However, when the Adv/cre vector was injected directly into specific regions of the adult brain, including the cerebral cortex, hippocampus, and cerebellum, recombination was detectable at the injection site. Furthermore, when the Adv/cre vector was injected into the forebrains of neonatal mice, the rearranged toxP locus from recombination could be detected in the injected regions for at least 8 weeks. Taken together, these results demonstrate that the Adv/cre vector expressing a functional cre protein is capable of mediating loxP-dependent recombination in various tissues and the recombined gene locus may in some cases be maintained for an extended period. The use of the adenovirus vector expressing cre combined with localized delivery to specific tissues may provide an efficient means to achieve conditional gene expression or knockout with precise spatiotemporal control.
Correction of the sickle cell disease mutation in human hematopoietic stem/progenitor cells (2015)

Sickle cell disease (SCD) is characterized by a single point mutation in the seventh codon of the β-globin gene. Site-specific correction of the sickle mutation in hematopoietic stem cells would allow for permanent production of normal red blood cells. Using zinc-finger nucleases (ZFNs) designed to flank the sickle mutation, we demonstrate efficient targeted cleavage at the β-globin locus with minimal off-target modification. By co-delivering a homologous donor template (either an integrase-defective lentiviral vector or a DNA oligonucleotide), high levels of gene modification were achieved in CD34(+) hematopoietic stem and progenitor cells. Modified cells maintained their ability to engraft NOD/SCID/IL2rγ(null) mice and to produce cells from multiple lineages, although with a reduction in the modification levels relative to the in vitro samples. Importantly, ZFN-driven gene correction in CD34(+) cells from the bone marrow of patients with SCD resulted in the production of wild-type hemoglobin tetramers.
Evidence for Ectopic Neurotransmission at a Neuronal Synapse (2005)

Neurotransmitter release is well known to occur at specialized synaptic regions that include presynaptic active zones and postsynaptic densities. At cholinergic synapses in the chick ciliary ganglion, however, membrane formations and physiological measurements suggest that release distant from postsynaptic densities can activate the predominantly extrasynaptic alpha7 nicotinic receptor subtype. We explored such ectopic neurotransmission with a novel model synapse that combines Monte Carlo simulations with high-resolution serial electron microscopic tomography. Simulated synaptic activity is consistent with experimental recordings of miniature excitatory postsynaptic currents only when ectopic transmission is included in the model, broadening the possibilities for mechanisms of neuronal communication.
Management of urea fertilizers (2015)

Sponsored by the Extension services of Illinios, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, and South Dakota in cooperation with the Extension Service, USDA, Washing, D.C.
Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practices (1975)

Incidence rates for 27 cancers in 23 countries and mortality rates for 14 cancers in 32 countries have been correlated with a wide range of dietary and other variables. Dietary variables were strongly correlated with several types of cancer, particularly meat consumption with cancer of the colon and fat consumption with cancers of the breast and corpus uteri. The data suggest a possible role for dietary factors in modifying the development of cancer at a number of other sites. The usefulness and limitations of the method are discussed.
His-384 Allotypic Variant of Factor H Associated with Age-related Macular Degeneration Has Different Heparin Binding Properties from the Non-disease-associated Form (2006)

A polymorphism in complement factor H has recently been associated with age-related macular degeneration (AMD), the leading cause of blindness in the elderly. A histidine rather than a tyrosine at residue position 384 in the mature protein increases the risk of AMD. Here, using a recombinant construct, we show that amino acid 384 is adjacent to a heparin-binding site in CCP7 of factor H and demonstrate that the allotypic variants differentially recognize heparin. This functional alteration may affect binding of factor H to polyanionic patterns on host surfaces, potentially influencing complement activation, immune complex clearance, and inflammation in the macula of AMD patients.
Practical limits of function prediction (2000)

The widening gap between known protein sequences and their functions has led to the practice of assigning a potential function to a protein on the basis of sequence similarity to proteins whose function has been experimentally investigated. We present here a critical view of the theoretical and practical bases for this approach. The results obtained by analyzing a significant number of true sequence similarities, derived directly from structural alignments, point to the complexity of function prediction. Different aspects of protein function, including (i) enzymatic function classification, (ii) functional annotations in the form of key words, (iii) classes of cellular function, and (iv) conservation of binding sites can only be reliably transferred between similar sequences to a modest degree. The reason for this difficulty is a combination of the unavoidable database inaccuracies and the plasticity of protein function. In addition, analysis of the relationship between sequence and functional descriptions defines an empirical limit for pairwise-based functional annotations, namely, the three first digits of the six numbers used as descriptors of protein folds in the FSSP database can be predicted at an average level as low as 7.5% sequence identity, two of the four EC digits at 15% identity, half of the SWISS-PROT key words related to protein function would require 20% identity, and the prediction of half of the residues in the binding site can be made at the 30% sequence identity level.
Cloning and expression of the cDNA for the murine interferon gamma receptor. (1989)

A murine interferon gamma (IFN-gamma) receptor cDNA was isolated by screening a murine T-cell hybridoma library prepared in lambda gt10 with probes prepared from a human IFN-gamma receptor cDNA. The 2.1-kilobase (kb) cDNA encoded a serine-rich polypeptide of 477 amino acids that was 52% identical to the human protein. Southern and Northern (RNA) blot analyses indicated the presence of a single receptor gene and a single predominant 2.3-kb receptor transcript. Human embryonic kidney fibroblasts, stably transfected with the murine IFN-gamma receptor cDNA, expressed murine IFN-gamma receptors as detected by flow cytometry with either ligand or a receptor-specific monoclonal antibody. Nontransfected cells bound neither ligand nor antibody. Radioligand-binding analysis demonstrated that the transfectants expressed 530,000 murine IFN-gamma receptors per cell and bound murine IFN-gamma with a Ka of 1 x 10(9) M-1. However, despite high-level expression of murine IFN-gamma receptors, the transfected human cells responded only to human and not to murine IFN-gamma as detected by enhancement of major histocompatibility class I antigen expression and induction of antiviral activity. These results thus document the isolation and expression of a full-length murine IFN-gamma receptor cDNA and suggest that additional species-specific components may be necessary to form a biologically active IFN-gamma receptor.
Plinabulin, a Distinct Microtubule-Targeting Chemotherapy, Promotes M1-Like Macrophage Polarization and Anti-tumor Immunity (2021)

Reprogramming tumor infiltrating myeloid cells to elicit pro-inflammatory responses is an exciting therapeutic maneouver to improve anti-tumor responses. We recently demonstrated that a distinct microtubule-targeting drug, plinabulin-a clinical-stage novel agent-modulates dendritic cell maturation and enhances anti-tumor immunity. Here, we investigated the effects of plinabulin on macrophage polarization <i>in vitro</i> and <i>in vivo</i>. Plinabulin monotherapy induced significant tumor growth inhibition in mice bearing subcutaneous MC38 colon cancer. Importantly, the regressing tumors were characterized by an increase in M1-like/M2-like tumor-associated macrophages (TAM) ratio. The efficacy of plinabulin remained unaltered in T cell-deficient Rag2<sup>-/-</sup> mice, suggesting an important role of macrophages in driving the drug's anti-tumor effect. Exposure of murine and healthy human macrophages to plinabulin induced polarization toward the M1 phenotype, including increased expression of co-stimulatory molecules CD80, CD86 and pro-inflammatory cytokines IL-1β, IL-6, and IL-12. M2-associated immunosuppressive cytokines IL-10 and IL-4 were reduced. This pro-inflammatory M1-like skewing of TAMs in response to plinabulin was dependent on the JNK pathway. Functionally, plinabulin-polarized human M1 macrophages directly killed HuT 78 tumor cells <i>in vitro</i>. Importantly, plinabulin induced a functional M1-like polarization of tumor infiltrating macrophages in murine tumors as well as in tumor samples from ovarian cancer patients, by preferentially triggering M1 proliferation. Our study uncovers a novel immunomodulatory effect of plinabulin in directly triggering M1 polarization and proliferation as well as promoting TAM anti-tumoral effector functions.
Identification of an immunodominant H‐2Db‐restricted CTL epitope of human PSA (2005)

We demonstrate that the psa65-73 peptide can be used for reactivation of PSA-specific CTLs in vitro and ex vivo, and H-2D(b) pentamers assembled with this peptide are an efficient tool for monitoring of PSA-specific CTL responses after DNA vaccination.
Policing the Immune System (2004)

In hopes of finding new remedies for ills including cancer and diabetes, scientists are following a band of elusive immune-cell cops whose existence was once hotly debated.
Measurement and significance of circulating natriuretic peptides in cardiovascular disease (1998)

1. The major cardiovascular and renal actions of alpha-atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and the fact that the heart is strategically located to sense changes in intravascular volume indicate the importance of these peptides in the overall control of the extracellular fluid volume under normal and pathophysiological conditions.2. This review examines the clinical and diagnostic significance of the measurement of plasma natriuretic peptides in diseases of the cardiovascular system with particular emphasis on the assessment of patients with heart failure. 3. Raised plasma levels of ANP and BNP have repeatedly been found in patients with heart disease originating from diverse causes including tachycardias, valvular stenosis or ventricular dysfunction. The raised circulating levels of natriuretic peptide (ANP, N-terminal proANP and BNP in particular) are associated with (i) raised atrial and pulmonary wedge pressures; (ii) reduced ventricular systolic and diastolic function; (iii) presence (and possibly geometric form) of left ventricular hypertrophy; and (iv) severe myocardial infarction. Although both plasma ANP and BNP are raised in the presence of left ventricular hypertrophy, BNP appears to be a better index of left ventricular hypertrophy.4. Several situations where the measurement of natriuretic peptides may be of benefit in the overall assessment of heart disease are discussed. However, it is emphasized that the measurement of plasma natriuretic peptides alone appears to be of limited value as a specific diagnostic tool, given that raised levels are a consequence of haemodynamic and structural abnormalities arising from diverse pathological processes. Despite these limitations, the major value of plasma natriuretic peptides in the examination of patients with suspected heart disease rests on the premise that: (i) a normal value would not be consistent with cardiac disease; (ii) the presence of markedly raised levels may help to target those for subsequent detailed assessment of underlying cardiac dysfunction; and (iii) markedly raised levels of plasma natriuretic peptides after myocardial infarction can identify those at high risk of death.