gebhart/patrepeval huggingface dataset:
Radioimmunotherapy of human colonic cancer xenografts with 90Y labeled monoclonal antibodies to carcinoembryonic antigen. (1988)

Monoclonal antibodies (MAbs) to carcinoembryonic antigen (CEA) or alpha-fetoprotein (AFP) were conjugated with diethylenetriaminepentaacetic acid and radiolabeled with 90Y at a specific activity of 4.0-6.0 mCi/mg. Approximately 50% of the radiolabeled anti-CEA antibody (90Y-labeled NP-2) bound to an immunoadsorbent containing CEA while analysis by high performance liquid chromatography revealed that 95-98% of the 90Y was associated with immunoglobulin. Less than 5% of the 90Y dissociated from either MAb after incubation in plasma for 48 h at 37 degrees C. After injection into nude mice, 98% of the circulating radioactivity remained associated with antibody and no loss of immunoreactivity was observed at 3 days. To evaluate 90Y-labeled NP-2 as a therapeutic agent, varied doses (10-100 microCi) were administered as a single i.v. injection into groups of nude mice bearing s.c. implants (0.3-0.4 g) of a CEA-producing human colonic cancer xenograft, GW-39. At the 10-microCi dose, no inhibition of tumor growth was observed. After 28 days, tumor growth was inhibited by as much as 77% in mice treated with 50 microCi of 90Y-labeled NP-2 as compared to tumor growth in control animals given 90Y-labeled anti-AFP. Doses higher than 50 microCi (75 and 100 microCi) were toxic to most of the animals, killing them within 2-3 weeks after administration. Marked suppression of circulating leukocytes was observed with 20 and 50 microCi by 1-2 weeks postinjection, but they returned to normal levels 3-4 weeks later. These studies show that treatment with 90Y-labeled MAbs against CEA can produce significant antitumor effects. However, toxicity to the bone marrow may limit the therapeutic efficacy of systemically administered 90Y-labeled MAbs.
Mouse VH7183 recombination signal sequences mediate recombination more frequently than those of VHJ558 (1995)

Abstract Mouse VH gene segments are conventionally classified into 13 families on the basis of sequence similarity. The 7183 family lies close to the 3’ end of the locus and is preferentially used in BALB/c mice; J558, the largest family, lies close to the 5’ end of the VH stretch and is preferentially used in C57BL/6 mice. To investigate whether differential effectiveness of the RSSs in the two families might contribute to the overusage of 7183 in the primary repertoire of BALB/c, we constructed recombination substrates in which the recombination signal sequences (RSSs) of VH segments 7183 and J558 compete with each other for a single RSS, DFL16.1, after transfection into two transformed cell lines derived from C57BL/6 and two cell lines from BALB/c mice. In both strains, the 7183 RSS was found to be preferentially used (83%). Thus, the 7183 RSS mediates recombination more frequently than does that of J558, and this preference must thereby influence the primary repertoire, but the strain difference cannot be accounted for by a difference in the RSSs.
Semaphorin3A, Neuropilin-1, and PlexinA1 Are Required for Lymphatic Valve Formation (2012)

Our data demonstrate an essential direct function of Sema3A-Nrp1-PlexinA1 signaling in lymphatic valve formation.
Insulin-like growth factor II mRNA expression in human breast cancer. (1988)

Insulin-like growth factor II is a growth factor important in fetal development. Several cancer tissues and cell lines have been reported to express IGF-II and rat IGF-II is mitogenic for breast cancer cell lines. Using Northern analysis and ribonuclease protection assays, IGF-II mRNA was detected in normal fibroblasts and in the established breast cancer cell line, T47D. In this cell line, steady state levels of IGF-II message were increased by treatment with estradiol. 10 nM IGF-II, purified from human serum, was mitogenic for breast cancer cell lines. In vitro, IGF-II may act as an autocrine growth factor for some cell lines. RNA derived from breast cancer, pathologically normal breast tissue, and benign breast disease also contained IGF-II mRNA. When paired samples of normal and cancer tissue were obtained from the breast of the same patient, the level of IGF-II mRNA expression in the normal tissue was at least that found in the cancer. This is consistent with previous observations that show IGF-II is expressed in mesenchyme. These findings suggest that in breast cancer IGF-II is produced by stromal tissue elements and potentially by the malignant epithelial cells. Therefore, IGF-II may function as an autocrine or a paracrine growth factor in different breast tumors.
Mapping and quantification of the major oligosaccharide components of heparin (1988)

A new method of determining the oligosaccharide composition of commercial glycosaminoglycan heparin is described in which heparin was first depolymerized using heparin lyase (EC 4.2.2.7), and then analysed by a single h.p.l.c. step. All 20 of the porcine and bovine heparins examined were found to contain a small number of major oligosaccharide components, which on average comprised 86% of their mass. The five most abundant oligosaccharides have defined chemical structures. Although the relative abundance of oligosaccharides varied, the heparins examined were surprisingly similar. Porcine, bovine, low-Mr, and high and low antithrombin III (ATIII)-affinity heparins, however, each had distinctly different proportions of these major oligosaccharide components. The concentrations of one of these five oligosaccharides, containing a portion of the ATIII binding site, correlated with the anticoagulant activity of the ATIII-affinity-fractionated porcine-mucosal heparins from which it was derived. An additional oligosaccharide of undetermined structure was found in significant quantities in both bovine heparin and high ATIII-affinity porcine-mucosal heparin. The correlation between oligosaccharide concentration and anticoagulant activity suggests that the oligosaccharide is derived from a structural variant of the ATIII-binding site. Finally, for the heparins examined chondroitin/dermatan sulphate formed 0.6-7.4% of their mass.
Factor X Nagoya 1 and Nagoya 2: a CRM– Factor X Deficiency and a Dysfunctional CRM+ Factor X Deficiency Characterized by Substitution of Arg306 by Cys and of Gly366 by Ser, respectively (1998)

We have identified, in two unrelated patients, factor X deficiency that we have designated factor X Nagoya 1 and Nagoya 2, respectively. The proband with factor X Nagoya 1 showed factor X activity level of 3% and factor X antigen level < 10% of the normal control value. All the exons and intron/exon junctions of the factor X gene were studied using a strategy combining polymerase chain reaction (PCR) amplification and nonradioactive single-strand conformational polymorphism (SSCP) analysis. Exon 8 containing DNA fragment of the proband with factor X Nagoya 1 showed aberrant migration on SSCP analysis. All exon-containing DNA fragments amplified by PCR were sequenced, and we identified a C-to-T substitution in exon 8 in the human factor X gene of the proband, which results in the replacement of Arg306 by Cys. This genetic defect has been transmitted from her father, and her sister also carried the same mutation; both showed almost half the normal levels of both factor X activity and antigen. The coordinates of human factor Xa indicated that Arg306 in the catalytic domain is positioned at the beginning of the alpha-helix near the second EFG-like domain. The substitution for Arg of Cys has been supposed to cause the destruction of local alpha-helix formation, possibly leading to the secretion problem. The proband with dysfunctional factor X Nagoya 2 was characterized by factor X activity level of 34% with normal factor X antigen level of 80%. We identified one substitution of G for A in exon 8 in the human factor X gene of the proband, which results in the replacement of Gly366 by Ser. As the Gly366 is positioned at the primary substrate binding pocket. the replacement of Gly with Ser would cause a defect of substrate binding, leading to the loss of enzymatic activity.
Effect of reinforcement volume fraction on mechanical alloying of Al–SiC nanocomposite powders (2007)

Mixtures of aluminium powder and nanoscaled SiC particles (n-SiC) at various volume fractions of 0, 1, 3, 5, 7 and 10 are comilled in a high energy planetary ball mill under an argon atmosphere to produce nanocrystalline Al–SiC nanocomposites. High resolution scanning electron microscopy (HRSEM), X-ray diffraction (XRD) method, laser particle size analysis and powder density measurement were used to study the morphological changes and microstructural evolution occurred during mechanical alloying. Al–SiC composite powder with microscaled SiC particles (1 m m) was also synthesised and characterised to examine the influence of reinforcement particle size on the milling process. It was found that with increasing volume fraction of n-SiC, a finer composite powder with more uniform particle size distribution is obtained. The morphology of the particles also became more equiaxed at shorter milling times. Furthermore, the analysis of XRD patterns by Williamson–Hall method indicated that the crystallite size of the aluminium matrix decreases with increasing reinforcement volume content while the lattice strain changes marginally. As compared with microscaled SiC particles, it appeared that the effect of n-SiC on the milling stages is more pronounced. The results clearly show that the reinforcement particles influence the work hardening and fracture of the metal matrix upon milling, affecting the structural evolution. With decreasing size of the ceramic particles to nanoscale, this influence becomes more pronounced as the surface to volume fraction increases.
Q and A: Climate Change (2010)

The need to urgently address the critical issue of climate change in Australia has once again been highlighted with the formation of the new federal government in Australia. Despite two decades of negotiations, virtually nothing has been done to address escalating global carbon emissions.
Creating a mobile web application platform (2009)

The software industry is currently in the middle of two transitions -- towards web-based software and towards web-enabled mobile devices. In this paper, we summarize our experiences in porting the Sun Labs Lively Kernel - an interactive web programming environment developed at Sun Microsystems Laboratories - onto a Nokia N810 mobile device. We report our experiences based on two different approaches that were used. First, we ported the system onto a regular web browser running in the mobile device. Second, we developed a custom-built native execution environment that provides more direct and extensive access to the underlying resources of the system. Based on these experiments, we will discuss the lessons learned as well as provide directions and guidance for future work.
Monitoring of patients for cytomegalovirus after organ transplantation by centrifugation culture and PCR (1992)

A modified centrifugation culture technique and a polymerase chain reaction (PCR) is described for detection of early antigen and IE antigen DNA, respectively, for rapid and sensitive monitoring of active cytomegalovirus (HCMV) infection after organ transplantation. In a preliminary study, 541 clinical specimens (blood, urine, bronchoalveolar lavage, pharyngeal wash, sputum) from 59 organ recipients were assayed for HCMV antigen by centrifugation culture; 144 samples were tested by PCR simultaneously. Antigenemia detected by centrifugation culture correlated strongly with active HCMV infection and clinical symptoms and proved useful for monitoring the efficacy of antiviral therapy. PCR was more sensitive in an earlier phase of infection when centrifugation culture was still negative. The clinical usefulness of both methods is discussed.
Learning to attend: Effects of practice on information selection (2009)

Though practice can lead to improved performance in many domains, it is currently unknown how practice affects the deployment of selective attention to filter distracting information. We conducted a series of experiments to address this issue by examining how performance on a task changed after repeated exposure to distractors. Distraction initially slowed response time during task performance, an effect that diminished with repeated exposure to the distractors. When the distractors were consistent in appearance, the practice effect developed quickly but was stimulus-specific. When the distractors were more variable in appearance, the practice effect developed slowly but transferred more readily to other conditions. These data indicate that practice with overcoming distraction leads to improvements in information filtering mechanisms that generalize beyond the training regimen when variable distractor stimuli are experienced.
On the mechanism of non-allelically excluded V alpha-J alpha T cell receptor secondary rearrangements in a murine T cell lymphoma. (1990)

We had previously demonstrated that several subclones derived from a CD3+, CD4-/CD8-, TCR-alpha beta+ murine T cell line have undergone secondary V alpha-J alpha rearrangements at the TCR-alpha locus (1). In an effort to examine the molecular mechanism responsible for these V alpha-J alpha replacements, the structures of TCR-alpha cDNA prepared from both the parental and subcloned T cell lines have been determined. Here we report that: 1) the mechanism whereby the secondary rearrangements occur is a precise deletion event that involves germ-line V alpha genes 5' to the preexisting V alpha-J alpha complex joining to J alpha segments 3' of the preexisting complex deleting the region in between, 2) preexisting productive V alpha-J alpha rearrangements of the parental line do not allelically exclude productive and nonproductive secondary rearrangements, 3) both productively rearranged TCR-alpha alleles of the parental cell line can undergo secondary rearrangements, 4) the presence of unrearranged germline V alpha transcripts in the parental line support an "accessibility" model of regulated lymphocyte receptor gene rearrangement. In addition, we present data which suggests that one of the subcloned lines has undergone a third rearrangement of one of its TCR-alpha alleles. One interpretation of these results is that T cells may have the ability to circumvent allelic exclusion at the TCR-alpha locus early in their ontogeny. This could provide T cells with an additional mechanism for generating an Ag receptor repertoire which is not found in B cells.
Multilevel approach to full-chip gridless routing (2001)

This paper presents a novel gridless detailed routing approach based on multilevel optimization. The multilevel framework with recursive coarsening and refinement in a V-shaped flow allows efficient scaling of our gridless detailed router to very large designs. The downward pass of recursive coarsening builds the representations of routing regions at different levels, while the upward pass of iterative refinement allows a gradual convergence to a globally optimized solution. The use of a multicommodity flow-based routing algorithm for the initial routing at the coarsest level and a modified maze algorithm for the refinement at each level considerably improves the quality of gridless routing results. Compared with the recently published gridless detailed routing algorithm using wire planning [1], our multilevel gridless routing algorithm is 3× to 75× faster. We also compared our multilevel framework with a recently developed three-level routing approach [1] and a traditional hierarchical routing approach. Our multilevel algorithm generates better detailed routing results with higher completion rates. To our knowledge, this is the first time that multilevel optimization has been applied to IC routing.
Effects of Glucagon-Like Peptide-1 in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction After Successful Reperfusion (2004)

When added to standard therapy, GLP-1 infusion improved regional and global LV function in patients with AMI and severe systolic dysfunction after successful primary angioplasty.
Preparation and evaluation of PEG-bound thrombin inhibitors based on 4-amidinophenylalanine. (1995)

The dipeptide Mtr-Asp-D-Adf-Pip 10 represents a potent thrombin inhibitor. In comparison to NAPAP, 10 exhibited improved tolerability and a longer half-life in vivo, i.e., 20 +/- 5 min. We have coupled aminopolyethyleneglycolmonomethylether of various molecular weights to the carboxyl moiety of 10 and evaluated their biological properties. First, Mtr-Asp-OBut was coupled to the amino group of the PEG employing TOTU as an activating agent. This was followed by the removal of the OBut protecting group and coupling of D-Adf-Pip using TOTU as well. The PEG-bound thrombin inhibitors showed inhibition constants vs. thrombin in the subnanomolar range, i.e., they were more active than the parent molecule 10. Moreover, the pegylated inhibitors exhibited a longer lasting effect in vivo. In rats the half-life of Mtr-Asn (PEG10000-OMe)-D-Adf-Pip 14 was determined to be 63 min. Mtr-Asn(PEG10000-OMe)-D-Adf-Pip 14 showed a half-life of 120 min in pigs. It could be concluded that these PEG-bound thrombin inhibitors may be employed as versatile drugs for parenteral administration in treating thrombotic disorders.
Structure, Function, and Insights into the Biosynthesis of a Head-to-Head Hydrocarbon in Shewanella oneidensis Strain MR-1 (2010)

A polyolefinic hydrocarbon was found in nonpolar extracts of Shewanella oneidensis MR-1 and identified as 3,6,9,12,15,19,22,25,28-hentriacontanonaene (compound I) by mass spectrometry, chemical modification, and nuclear magnetic resonance spectroscopy. Compound I was shown to be the product of a head-to-head fatty acid condensation biosynthetic pathway dependent on genes denoted as ole (for olefin biosynthesis). Four ole genes were present in S. oneidensis MR-1. Deletion of the entire oleABCD gene cluster led to the complete absence of nonpolar extractable products. Deletion of the oleC gene alone generated a strain that lacked compound I but produced a structurally analogous ketone. Complementation of the oleC gene eliminated formation of the ketone and restored the biosynthesis of compound I. A recombinant S. oneidensis strain containing oleA from Stenotrophomonas maltophilia strain R551-3 produced at least 17 related long-chain compounds in addition to compound I, 13 of which were identified as ketones. A potential role for OleA in head-to-head condensation was proposed. It was further proposed that long-chain polyunsaturated compounds aid in adapting cells to a rapid drop in temperature, based on three observations. In S. oneidensis wild-type cells, the cellular concentration of polyunsaturated compounds increased significantly with decreasing growth temperature. Second, the oleABCD deletion strain showed a significantly longer lag phase than the wild-type strain when shifted to a lower temperature. Lastly, compound I has been identified in a significant number of bacteria isolated from cold environments.
Role of cranberry juice on molecular‐scale surface characteristics and adhesion behavior of Escherichia coli (2005)

Cranberry juice has long been believed to benefit the prevention and treatment of urinary tract infections (UTIs). As the first step in the development of infection, bacterial adhesion is of great research interest, yet few studies have addressed molecular level adhesion in this context. P-fimbriated Escherichia coli play a major role in the development of a serious type of UTI, acute pyelonephritis. Experiments were conducted to investigate the molecular-scale effects of cranberry juice on two E. coli strains: HB101, which has no fimbriae, and the mutant HB101pDC1 which expresses P-fimbriae. Atomic force microscopy (AFM) was used to investigate both bacterial surface characteristics and adhesion forces between a probe surface (silicon nitride) and the bacteria, providing a direct evaluation of bacterial adhesion and interaction forces. Cranberry juice affected bacterial surface polymer and adhesion behavior after a short exposure period (<3 h). Cranberry juice affected the P-fimbriated bacteria by decreasing the adhesion forces between the bacterium and tip and by altering the conformation of the surface macromolecules on E. coli HB101pDC1. The equilibrium length of polymer (P-fimbriae) on this bacterium decreased from approximately 148 to approximately 48 nm upon being exposed to cranberry juice. Highly acidic conditions were not necessary for the prevention of bacterial adhesion, since neutralization of cranberry juice solutions to pH = 7.0 allowed us to observe differences in adhesion between the E. coli strains. Our results demonstrate molecular-level changes in the surfaces of P-fimbriated E. coli upon exposure to neutralized cranberry juice.
Simple micropatterning of biomolecules on a diazoketo-functionalized photoresist (2008)

A simple strategy for the patterning of cells and biomolecules including DNA and protein was developed, employing novel diazoketo-functionalized photoresists in conjunction with a simplified lithographic process that does not require photoacid generator, post-exposure bake or development steps. The diazoketo functional groups present in the polymers undergo Wolff rearrangement upon UV light irradiation to generate carboxylic groups. This chemistry was used to create patterns of alternate hydrophilic/hydrophobic regions on the surface of diazoketo-functionalized polymers. The in vitro cell culture on the patterned surfaces of the polymer showed good alignment of cells on the UV-exposed regions, where carboxylic groups were predominant. Furthermore, cells were found to maintain their alignment during proliferation. In addition to this, the photogeneration of carboxylic groups by diazoketo functional groups was exploited for DNA and streptavidin patterning. For DNA patterning, amine-modified probe DNA was successfully immobilized on the photopatterned regions of the polymer by amide bond formation using EDC/NHS coupling chemistry. Successful hybridization with complementary DNA proved the selectivity and functionality of the immobilized probe DNA. Biotin-amine was also immobilized on the photopatterned regions of the diazoketo-functionalized polymer in a similar manner to that of probe DNA to study streptavidin patterning. Biotin-specific streptavidin binding proved the successful patterning of biotin-amine by amide bond formation. These results showed that diazoketo-functionalized photoresist is biocompatible and simple to use for biomolecular patterning, which can be used in further approaches for high-throughput screening assays.
Classical and Alternative Pathways of Mast Cell Activation (2002)

It has long since been recognized that mast cells are critical effectors of anaphylactic reactions, and the existence of these potentially hazardous cells has solely been justified due to their beneficial role in some infections with extracellular parasites. A novel understanding of mast cells as sentinels of the immune system has been made possible by taking advantage of mast cell-deficient mice in order to study the roles of mast cells in vivo and by detailed analyses of mast cell activation in vitro. Collectively, these experiments have revealed a variety of IgE-independent stimuli, which lead to the activation of mast cells as crucial initiators of an inflammatory response. Besides their effector function, a variety of studies reviewed herein point towards important regulatory roles for mast cells, especially regarding their interaction with other cell types.
In Vivo Growth Factor Treatment of Degenerated Intervertebral Discs (2004)

Anular fibrochondrocytes in degenerated discs are responsive to some growth factors in vivo. The results have implications in the early intervention of disc degeneration to arrest or slow the degenerative process.