gebhart/patrepeval huggingface dataset:
Controlled release of plasmid DNA from biodegradable scaffolds fabricated using a thermally-induced phase-separation method (2004)

Highly porous poly(D,L-lactic-co-glycolic acid) (PLGA) scaffolds were fabricated by a thermally-induced phase-separation (TIPS) method to deliver plasmid DNA in a controlled manner. A variety of TIPS parameters directly affecting pore structures and their interconnectivities of the scaffold, such as polymer concentration, solvent/non-solvent ratio, quenching methods and annealing time, were systematically examined to explore their effects on sustained release behaviors of plasmid DNA. Plasmid DNA was directly loaded into the inner pore region of the scaffold during the TIPS process. By optimizing the parameters, PLGA scaffolds releasing plasmid DNA over 21 days were successfully fabricated. DNA release profiles were mainly affected by the pore structures and their interconnectivities of the scaffolds. Plasmid DNA released from the scaffolds fully maintained its structural integrity and showed comparable transfection efficiency to native plasmid DNA. These biodegradable polymeric scaffolds capable of sustained DNA release can be potentially applied for various tissue engineering purposes requiring a combined gene delivery strategy.
Ovarian cancer identification based on dimensionality reduction for high-throughput mass spectrometry data (2005)

The software is available for academic and non-commercial institutions.
Higher-order functions for parsing (1992)

Abstract In combinator parsing , the text of parsers resembles BNF notation. We present the basic method, and a number of extensions. We address the special problems presented by white-space, and parsers with separate lexical and syntactic phases. In particular, a combining form for handling the ‘offside rule’ is given. Other extensions to the basic method include an ‘into’ combining form with many useful applications, and a simple means by which combinator parsers can produce more informative error messages.
Infliximab in Pediatric Ulcerative Colitis: Two-year Follow-up (2004)

Infliximab is associated with short- and long-term clinical improvement in children and adolescents with moderate to severe UC.
FcγRIIA H/R131 Polymorphism, Subclass-Specific IgG Anti-Heparin/Platelet Factor 4 Antibodies and Clinical Course in Patients With Heparin-Induced Thrombocytopenia and Thrombosis (1997)

The explanation why only a subset of patients with heparin-induced thrombocytopenia (HIT) develop clinically apparent thromboses (HITT) remains uncertain. It has been proposed that platelet activation induced by cross-linking of Fc gamma RIIA by anti-heparin/platelet factor 4 (PF4) antibodies is central to the pathogenesis of thrombosis. The observation that a common functional polymorphism of Fc gamma RIIA, involving either an arginine (R) or histidine (H) at amino acid 131, may underlie disease susceptibility prompted us to investigate the prevalence of receptor isoforms in patients with HIT and HITT. Furthermore, because these isoforms reportedly differ in their avidity for immune complexes containing human IgG2, we also analyzed sera from patients with HIT and HITT for the prevalence of various subclass-specific IgG anti-heparin/PF4 antibodies. No difference in the allele frequency of Fc gamma RIIA-H131 or R131 was identified among 13 patients with HIT or 23 with HITT compared with 102 controls (chi 2 = 1.21, P = .8). Furthermore, although most patients had IgG2 antibodies (62%), IgG, was the predominant subclass in 30 of the 34 patients with IgG anti-heparin/PF4 antibodies and in 12 was the exclusive subclass found. Also, there was no association between the concordance of IgG2 anti-heparin/ PF4 antibodies and the expression of Fc gamma RIIA-H131 in patients with HITT compared with patients with thrombocytopenia alone. These results make it unlikely that the Fc gamma RIIA-H131 isoform or IgG2 anti-heparin/PF4 antibodies are required to develop HITT, suggesting that factors in addition to cross-linking of Fc gamma RIIA receptors contribute to the pathogenesis of thrombosis in patients with heparin-dependent antiplatelet: antibodies.
Synthesis and Ring Transformation of Pyrrolo[2,3‐d][1,3]oxazine to Pyrrolo[2,3‐d]Pyrimidines (1992)

Abstract A convenient route is reported for the synthesis of fused pyrrolo[2,3‐ d ][1,3]oxazine and pyrrolo[2,3‐ d ]‐pyrimidine derivatives from 2‐amino‐1‐benzyl‐3‐ t ‐butoxycarbonyl]‐4,5‐dimethylpyrrole.
Characterization of Human Atherosclerosis by Optical Coherence Tomography (2002)

Objective OCT criteria are highly sensitive and specific for characterizing different types of atherosclerotic plaques. These results represent an important step in validating this new intravascular imaging modality and will provide a basis for the interpretation of intracoronary OCT images obtained from patients.
Detection of calcium gradients in live ex vivo human epidermis using a novel approach based on phasor analysis of two-photon excitation Fluorescence Lifetime Imaging (FLIM) (2009)

Detection of calcium gradients in live ex vivo human epidermis using a novel approach based on phasor analysis of two-photon excitation Fluorescence Lifetime Imaging (FLIM) A Celli, 1 SA Sanchez, 2 M Behne, 3 T Hazelet, 2 E Gratton 2 and T Mauro 1 1 Dermatology, VAMC- UCSF, San Francisco, CA, 2 Biomedical Engeneering, University of California Irvine, Irvine, CA and 3 Dermatology and Venerology, University Hospital Hamburg-Eppendorff, Hamburg, Germany Ionic gradients are found across a variety of tissues, and control vital functions in skin. It has been difficult to accurately measure whole tissue ionic gradients in vivo, as previous methods have been ill-suited to address problems of tissue thickness, concentration artifacts, and calibration across inhomogeneous tissue. Here we show that a novel, minimally invasive, experimental and analytic imaging approach accurately quantifies and localizes the free Ca2+ gradient in ex vivo epidermis and dermis, and allows simultaneous analysis of epidermal morphology and Ca2+ concentrations in the same samples. This method is based on the combination of two-photon excitation fluores- cence lifetime imaging (FLIM) and a novel data analysis technique based on the phasor represen- tation of the FLIM data (Digman et al 2008). Skin samples from adult patients were incubated with the fluorescent calcium sensitive dye Calcium Green 5N (CG5N) whose lifetime is sensitive to vari- ation in calcium concentrations. The use of two-photon excitation provides high axial and lateral spatial resolution, deep tissue penetration, and low out of focus photodamage, while the phasor plot analysis allows calibrating the response of the dye to calcium directly in tissue. The high spa- tial resolution offered by this method and the data analysis performed allowed us to measure intracellular average calcium concentrations directly in tissue and detect a previously unknown bimodal distribution of Ca2+ concentrations in the proliferative epidermal basal layer. This approach reveals that the extracellular space in epidermis is much narrower than previously thought, local- izes most epidermal Ca2+ to intracellular stores. These new findings suggest that long-held hypothe- ses addressing Ca2+ control of differentiation and barrier formation require revision.
Segmentation of Osteoarthritic Femoral Cartilage Using Live Wire (2000)

introduction Magnetic resonance imaging (MRI) has become an important non-invasive technique for quantitative assessment of volume and thickness of the articular cartilage [I, 21. Both parameters have great potential for monitoring progression of disease in patients with osteoarthritis and for evaluating therapeutic response, e.g. in cartilage transplants. A very important but also tedious and time-consuming part of the post-processing of MRI data is the identification of the voxels that constitute the cartilage. For this task of segmentation different methods have been introduced with the goal to reduce the amount of necessary user interaction and thereby to increase reproducibility and accuracy [3, 41. While these techniques have been shown to be accurate in normal subjects, they may be limited for segmenting diseased cartilage with inhomogeneous texture and irregular and interrupted contours, as is typical in MR images of diseased knees with advanced osteoarthritis. The purpose of this work was to assess the feasibility of cartilage segmentation in MR images from patients with osteoarthritis using a combination of a Kuwahara smoothing filter [5] and an adaptation of Live Wire, a widely configurable and hence very flexible segmentation method [6].
Cequent Pharmaceuticals, Inc.: The Biological Pitcher for RNAi Therapeutics (2007)

Cequent Pharmaceuticals, Inc. is a recently established biopharmaceutical company that aims to develop clinically compatible therapies based on RNAi, a potent gene-silencing mechanism discovered in 1998. The company's proprietary technology, transkingdom RNAi (tkRNAi), uses nonpathogenic bacteria to produce and deliver shRNA into target cells to induce RNAi. Our initial focus is on the development of a tkRNAi-based therapy for familial adenatomous polyposis, an inherited form of colon cancer. Cequent's first tkRNAi-based drug for familial adenatomous polyposis, CEQ501, is currently in advanced preclinical testing. As part of its ongoing activities, Cequent plans to develop additional tkRNAi-based products for indications within and outside the GI tract. Our overall goal is to establish tkRNAi as a platform for developing a wide range of RNAi-based therapies.
RADIOIMMUNOASSAY FOR THE MEASUREMENT OF ADENOSINE 3′,5′-CYCLIC PHOSPHATE (1969)

A sensitive and specific radioimmunoassay for adenosine 3',5'-cyclic phosphate (cyclic AMP) has been developed which allows measurement of the nucleotide in extracts of 5-10 mg of tissue. The radioimmunoassay is sufficiently specific for cyclic AMP to eliminate the need for prior chromatographic separation of the cyclic nucleotide from other tissue nucleotides. The radioimmunoassay system is based upon competition of cyclic AMP with a labeled cyclic AMP derivative of high specific activity for binding sites on an antibody specific for the cyclic nucleotide. Antibody to cyclic AMP was obtained by immunizing rabbits with an antigen prepared by conjugating succinyl cyclic AMP with human serum albumin. A high specific activity derivative of cyclic AMP was prepared by synthesizing succinyl cyclic AMP tyrosine methyl ester (SCAMP-TME) and iodinating the phenolic hydroxyl group of the tyrosine moiety with (125)I. Free and antibody-bound (125)I-SCAMP-TME were separated by precipitation of the antibody-bound fraction with a second antibody (goat anti-rabbit gamma globulin). Displacement of (125)I-SCAMP-TME by unlabeled cyclic AMP when plotted as a semilogarithmic function was linear over a concentration range of 2-100 picomoles. The specificity of the antibody was tested against structurally related nucleotides, nucleosides, and purine bases. All had less than 0.005 per cent of the potency of cyclic AMP in inhibiting (125)I-SCAMP-TME binding. The marked differences in affinity of the various cyclic nucleotides to cyclic AMP antibody would suggest that antibodies can be developed for each of the cyclic nucleotides by the principles used in this work.
Topotecan Dosing Guidelines in Ovarian Cancer: Reduction and Management of Hematologic Toxicity (2004)

Topotecan dosing considerations and alternative dosing schedules to reduce and manage myelosuppression during the treatment of relapsed ovarian cancer were reviewed. The myelosuppression patterns from phase I, II, and III clinical trials were analyzed to evaluate the degree of hematologic toxicity and to determine risk factors predictive of myelosuppression. Additionally, recent publications of alternative topotecan doses and schedules were examined. Extent of prior therapy, prior platinum therapy (particularly carboplatin), advanced age, impaired renal function, and prior radiation therapy were identified as potential risk factors for greater hematologic toxicity after topotecan therapy. Reducing the starting topotecan dose to 1.0 or 1.25 mg/m2/day is recommended to reduce the incidence of severe myelosuppression in high-risk individuals receiving topotecan for 5 consecutive days. Hematopoietic growth factors, transfusion therapy, and schedule adjustments may also help manage myelosuppression. Alternative schedules of 3-day or weekly dosing appear to have less myelotoxicity and are currently under evaluation. The clinical aspects of topotecan-related myelosuppression and results from clinical trials indicate that the dose, and possibly the dosing schedule, of topotecan can be modified to reduce hematologic toxicity and improve tolerance without compromising efficacy. Prospective individualization of topotecan dosing may prevent or minimize dose-limiting myelosuppression and allow patients to achieve the maximum topotecan benefit by improving their ability to complete therapy with fewer treatment delays. Ongoing clinical trials evaluating alternative dosing schedules with superior hematologic tolerability may facilitate the inclusion of topotecan in combination regimens for patients with ovarian cancer. Proposed topotecan dosing guidelines to reduce and manage myelosuppression are outlined.
Insecticidal RNA, the long and short of it (2015)

Transgenic plants that express insect-specific RNA in chloroplasts kill pests through RNA interference [Also see Report by Zhang et al. ]
Chromosomal localization of glutamate receptor genes: relationship to familial amyotrophic lateral sclerosis and other neurological disorders of mice and humans. (1993)

Receptors for the major excitatory neurotransmitter glutamate may play key roles in neurodegeneration. The mouse Glur-5 gene maps to chromosome 16 between App and Sod-1. The homologous human GLUR5 gene maps to the corresponding region of human chromosome 21, which contains the locus for familial amyotrophic lateral sclerosis. This location, and other features, render GLUR5 a possible candidate gene for familial amyotrophic lateral sclerosis. In addition, dosage imbalance of GLUR5 may have a role in the trisomy 21 (Down syndrome). Further characterization of the murine glutamate receptor family includes mapping of Glur-1 to the same region as neurological mutants spasmodic, shaker-2, tipsy, and vibrator on chromosome 11; Glur-2 near spastic on chromosome 3; Glur-6 near waltzer and Jackson circler on chromosome 10; and Glur-7 near clasper on chromosome 4.
An analysis of TCP processing overhead (2003)

The authors report a preliminary analysis of the processing overhead of the transport protocol TCP (Transmission Control Protocol) in which they estimate the possible performance range of the protocol. The analysis was performed by compiling a version of TCP and counting the number of the instructions in the common path. The analysis suggests that fewer than 200 instructions are required to process a TCP packet in the normal case. This number is small enough to support very high-speed transmission if it were the major overhead. The authors offer some speculations about the actual source of processing overhead in network protocols.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Thrombopoietin, flt3‐ligand and c‐kit‐ligand modulate HOX gene expression in expanding cord blood CD133+ cells (2004)

Haemopoietic stem/progenitor cell (HSPC) development is regulated by extrinsic and intrinsic stimuli. Extrinsic modulators include growth factors and cell adhesion molecules, whereas intrinsic regulation is achieved with many transcription factor families, of which the HOX gene products are known to be important in haemopoiesis. Umbilical cord blood CD133+ HSPC proliferation potential was tested in liquid culture with 'TPOFLK' (thrombopoietin, flt-3 ligand and c-kit ligand, promoting HSPC survival and self-renewal), in comparison to 'K36EG' (c-kit-ligand, interleukins-3 and -6, erythropoietin and granulocyte colony-stimulating factor, inducing haemopoietic differentiation). TPOFLK induced a higher CD133+ HSPC proliferation (up to 60-fold more, at week 8) and maintained a higher frequency of the primitive colony-forming cells than K36EG. Quantitative polymerase chain reaction analysis revealed opposite expression patterns for specific HOX genes in expanding cord blood CD133+ HSPC. After 8 weeks in liquid culture, TPOFLK increased the expression of HOX B3, B4 and A9 (associated with uncommitted HSPC) and reduced the expression of HOX B8 and A10 (expressed in committed myeloid cells) when compared to K36EG. These results suggest that TPOFLK induces CD133+ HSPC proliferation, self-renewal and maintenance, up-regulation of HOX B3, B4 and A9 and down-regulation of HOX B8 and A10 gene expression.
The binding of fucose-containing glycoproteins by hepatic lectins. The binding specificity of the rat liver fucose lectin. (1986)

The parameters that affect the interaction of ligands with a fucose-binding lectin from rat liver have been examined. 125I-Fucosyl-bovine serum albumin (Fuc-BSA) containing 50 residues of fucose/molecule was used as the standard ligand. At low initial concentrations of ligand (10 ng/ml) and lectin (140 ng/ml), the reaction reaches equilibrium at pH 7.8, 23 degrees C, within 40 min. The binding of ligands is Ca2+ dependent with half-maximal binding occurring at 54 microM Ca2+; of several metal ions tested, only Sr2+ partially replaced Ca2+. Binding was maximal between pH 7.6 and 8.6, fell slightly up to pH 10, but fell markedly below pH 7. The lectin-ligand complexes dissociated at low pH, on removal of Ca2+, or in the presence of a large excess of competing ligand. The apparent association constant (Ka) for Fuc-BSA was 1.75 X 10(8) M-1. The fucose content of the Fuc-BSA also influenced binding, with little apparent binding below 24 fucose residues/molecule and maximal binding from 40 to 50 fucose residues/molecule. With knowledge of the parameters influencing binding, sensitive reproducible assays for the lectin were developed. The binding specificity of the lectin was examined by measuring the inhibition of 125I-Fuc-BSA binding by neoglycoproteins, monosaccharides, and glycosides or by direct binding of neoglycoproteins. Galactosides and beta-linked fucosides were the best ligands among the neoglycoproteins, with much weaker binding by mannosyl- or N-acetylglucosaminyl-BSA. On the basis of the pattern of inhibition of Fuc-BSA binding by various monosaccharides and glycosides, it is possible to propose the conformations of saccharides that best fit the lectin-binding site. The C1 conformation of N-acetyl-D-galactosamine fits best, although other not obviously related monosaccharides such as L-fucose, L-arabinose, and D-mannose can also assume conformations that permit them to be effective inhibitors. The pattern of binding of neoglycoproteins to the lectin differs from that of other pure hepatic lectins. Thus, the fucose lectin has a high affinity for Fuc-BSA and galactosyl-BSA but a low affinity for N-acetylglucosaminyl-BSA. The galactose lectin binds only galactosyl-BSA and shows little binding with either N-acetylglucosaminyl-BSA or Fuc-BSA. In contrast, the mannose/N-acetylglucosamine lectin binds N-acetylglucosaminyl-BSA and Fuc-BSA but not galactosyl-BSA.
Exonuclease cycling assay: an amplified assay for the detection of specific DNA sequences. (1992)

An assay is described in which an oligonucleotide probe is specifically digested by lambda exonuclease only when it is annealed to its complementary sequence. In this assay, a cycling effect occurs whereby a small amount of target sequence acts as a specific co-factor in the enzymatic degradation of a larger number of molecules of an oligonucleotide probe. This amplification principle is demonstrated and the effect of the oligonucleotide probe sequence investigated. The necessary steps needed to convert this effect into a useful diagnostic tool are discussed.
Purified Fumonisin B1 Decreases Cardiovascular Function but Does Not Alter Pulmonary Capillary Permeability in Swine (2000)

Fumonisins are mycotoxins produced by Fusarium verticillioides, which induce acute pulmonary edema in swine. We previously reported that ingestion of fumonisin-containing culture material decreases cardiovascular function in swine (1996,a,b; Fundam. Appl. Toxicol. 31, 169-172; 33, 140-148; 1999, Am. J Vet. Res. 60, 1291-1300). The main purpose of this study was to confirm that fumonisin B(1) was responsible for the observed cardiovascular changes. Treated pigs (n = 6) were given daily intravenous injections of purified fumonisin B(1) at 1 mg/kg for 4 days, while controls (n = 6) were injected with equal volumes of saline. On day 5, pigs were anesthetized with butorphanol-chloralose and instrumented for hemodynamic studies. Terminally, bronchoalveolar lavage was performed on each pig to determine the relative permeability index of the pulmonary endothelium. Fumonisin B(1)-treated pigs had marked decreases in the maximal rate of change of left ventricular pressure (dP/dt(max)), mean aortic pressure, cardiac output, and arterial pO(2), accompanied by increases in mean pulmonary artery pressure, oxygen extraction ratio, and blood hemoglobin concentration. Plasma and left ventricular sphingosine and sphinganine concentrations were markedly increased in treated pigs at day 5; however, there was no difference in the relative permeability index between groups. Serum cholesterol concentrations and activities of hepatic-derived enzymes were increased, and hepatocyte apoptosis and mitoses were present in the livers of fumonisin-treated pigs. In the lungs of treated pigs, there was proteinaceous edema and membranous accumulations in capillary endothelial cells. These results indicate that cardiovascular function is altered by fumonisin B(1), and that fumonisin-induced pulmonary edema is caused by left-sided heart failure and not by altered endothelial permeability. Because of the potential for contamination of human foodstuffs by fumonisins, the cardiovascular toxicity of these compounds must be taken into consideration.
PKCι Maintains a Tumor-initiating Cell Phenotype That Is Required for Ovarian Tumorigenesis (2013)

PKCι drives a tumor-initiating cell phenotype in ovarian cancer cells that can be therapeutically targeted with auranofin, a small molecule inhibitor of PKCι signaling.
Analgesics of the orvinol type. 19-Deoxy and 6,20-epoxy derivatives (1984)

A series of new ethenotetrahydrooripavine derivatives has been prepared in which the C-19 hydroxyl group has been replaced by hydrogen. The syntheses proceed via the thioanisole adducts of the thevinones. These adducts are converted to 1,2-epoxides, which are rearranged to aldehydes and then reduced to primary alcohols. Further conversion of these alcohols result in the deoxy derivatives and the 6,20-epoxy analogues, which contain a fused tetrahydrofuran ring. The compounds in this series, some of which offer the possibility of strong hydrogen-bonding interactions and others of which contain sterically fixed lipophilic side chains, have been evaluated as analgesics by the rat tail-flick method. Based on these and previous results, a proposal is made for the interaction of the orvinols with the opiate receptor involving both lipophilic (L) and hydrophilic (H) subsites. This proposal can be extended to suggest an optimum conformation for the enkephalins.