gebhart/patrepeval huggingface dataset:
Graphical Access to Medical Expert Systems: I. Design of a Knowledge Engineer’s Interface (1986)

Summary Optimal construction of medical expert systems demands a powerful interactive environment for knowledge base management by knowledge engineers. Key requirements include techniques for (a) examining existing information, (b) adding new knowledge and editing preexisting data structures, and (c) examining dynamic internal system behavior to facilitate debugging during consideration of actual cases. This article addresses design considerations in the development of such knowledge engineering tools. The emphasis is on the use of professional workstations with high density graphics interfaces since that technology is rapidly becoming a predominant environment for knowledge engineering activities. To illustrate the points made, examples are drawn from an experimental knowledge base management tool designed for knowledge engineers constructing the knowledge base of ONCOCIN, an expert system to advise in the management of cancer patients.
Production of highly homogeneous and structurally intact recombinant von Willebrand factor multimers by furin‐mediated propeptide removal in vitro (1996)

Recombinant human von Willebrand Factor (rvWF), a multimeric glycoprotein essential to haemostasis, has been developed as a potential therapeutic agent for treatment of von Willebrand disease (vWD). Permanent Chinese-hamster ovary (CHO)-rvWF cell clones co-expressing recombinant furin (rfurin) were established in order to ensure complete rvWF propeptide removal [Fischer, Schlokat, Mitterer, Reiter, Mundt, Turecek, Schwarz and Dorner (1995) FEBS Lett. 375, 259-262]. Large quantities of material are required for in vivo tests and clinical studies. This demand is commonly met by achieving high-yield expression of the desired protein via amplification. Co-amplification of rfurin, necessary to completely process increasing amounts of rvWF precursor, could not be accomplished, presumably due to lethal effects of overexpressed rfurin for the host cells [Creemers (1994) Ph.D. Thesis, University of Leuven]. Recent reports have inferred that rfurin can only mediate rvWF processing intracellularly [Rehemtulla and Kaufman (1992) Blood 79, 2349-2355; Rehemtulla, Dorner and Kaufman (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 8235-8239]. We report here that rvWF-precursor processing, however, occurs predominantly extracellularly upon rfurin co-expression. Mixing experiments employing rfurin- as well as rvWF-precursor-containing conditioned media demonstrate that rvWF precursors are accessible and cleavable by rfurin in vitro. Exposure to rfurin in vitro converts the heterogeneous multimer pattern typical of incompletely processed rvWF multimers into highly homogeneous and structurally intact multimers superior to the ones exhibited by plasma-derived vWF. These findings thus demonstrate the feasibility of large-scale production of a completely processed, intact and homogeneous rvWF preparation, based on individual rvWF-precursor high-yield expression and subsequent propeptide removal by rfurin in vitro.
Aroylations of β-Diketones at the Terminal Methyl Group to Form 1,3,5-Triketones. Cyclizations to 4-Pyrones and 4-Pyridones (1960)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAroylations of β-Diketones at the Terminal Methyl Group to Form 1,3,5-Triketones. Cyclizations to 4-Pyrones and 4-PyridonesROBLEY J. LIGHT and CHARLES R. HAUSERCite this: J. Org. Chem. 1960, 25, 4, 538–546Publication Date (Print):April 1, 1960Publication History Published online1 May 2002Published inissue 1 April 1960https://pubs.acs.org/doi/10.1021/jo01074a013https://doi.org/10.1021/jo01074a013research-articleACS PublicationsRequest reuse permissionsArticle Views613Altmetric-Citations69LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Sequence determinants of the capping box, a stabilizing motif at the N‐termini of α‐helices (1994)

The capping box, a recurrent hydrogen bonded motif at the N-termini of alpha-helices, caps 2 of the initial 4 backbone amide hydrogen donors of the helix (Harper ET, Rose GD, 1993, Biochemistry 32:7605-7609). In detail, the side chain of the first helical residue forms a hydrogen bond with the backbone of the fourth helical residue and, reciprocally, the side chain of the fourth residue forms a hydrogen bond with the backbone of the first residue. We now enlarge the earlier definition of this motif to include an accompanying hydrophobic interaction between residues that bracket the capping box sequence on either side. The expanded box motif--in which 2 hydrogen bonds and a hydrophobic interaction are localized within 6 consecutive residues--resembles a glycine-based capping motif found at helix C-termini (Aurora R, Srinivasan R, Rose GD, 1994, Science 264:1126-1130).
Involvement of the hypothalamic-pituitary-adrenal/gonadal axis and the peripheral nervous system in rheumatoid arthritis: Viewpoint based on a systemic pathogenetic role (2001)

From the compendium presented above, the following statements become evident: 1) Inappropriately low secretion of cortisol in relation to inflammation is a typical feature of the inflammatory disease in patients with RA. 2) The secretion of adrenal androgens is significantly reduced, which is a problem in postmenopausal women and elderly men due to a lack of downstream sex hormones. 3) Serum levels of testosterone are markedly reduced in RA. 4) Sympathetic nerve fibers are markedly reduced in the synovial tissue of patients with RA, whereas proinflammatory sensory fibers (substance P) are present. 5) Substance P serves to continuously sense painful stimuli in the periphery, and the nociceptive input from the inflamed joint shows a large amplification in the spinal cord. This leads to continuous pain with stabilization of the afferent sensory input and continuous release of proinflammatory substance P into the lumen of the joint. From these facts it is obvious that alterations of the systemic antiinflammatory feedback systems contribute significantly to the pathogenesis of RA. Disease therapy directed at these alterations must provide a mechanism to replace the adrenal glands (glucocorticoids), the gonadal glands (androgens), and the sympathetic nervous system (adenosine increase by low-dose MTX, sulfasalazine, and salicylates) in order to integrate their immunosuppressive effects at the local site of synovial inflammation. Although local processes of the adaptive immune system are important in pathogenesis in the acute phase of RA, these mechanisms may be less important during the chronic phase of the disease in the absence of a specific trigger. We believe that a defect of systemic antiinflammatory feedback systems is an important factor in the perpetuation of RA. This review reinforces the belief that combined therapeutic approaches on a neuroendocrine immune basis are of crucial importance in a pathogenetically oriented therapy of RA.
Pharmacologic Treatment of Eating Disorders (2002)

Continued research efforts are necessary, particularly regarding the long-term effects of therapy and the development of new pharmacologic strategies.
Comparison of angiogenesis-related factor expression in primary tumor cultures under normal and hypoxic growth conditions (2008)

As linear correlations exist between expression levels of angiogenic factors under normoxic and hypoxic conditions in vitro, we propose that explanted primary cells may be used to probe the in vivo hypoxic environment. Furthermore, differential expression levels for each sample across all proteins examined suggests it may be possible to build a predictor for angiogenesis-related anticancer agents, as each sample has a unique expression profile. Further studies should be performed to correlate in vitro protein expression levels of angiogenesis-related factors with in vivo patient response.
HIV Type 1 Tat Protein Induces Apoptosis and Death in Jurkat Cells (1995)

Jurkat cells stably expressing high levels of the HIV-1 Tat protein were generated after transfection with an Epstein-Barr virus-based episomal replicon and selection in hygromycin B. The Jurkat Tat transfectants exhibited a longer doubling time when compared to Jurkat cells or Jurkat cells transfected with the control parent plasmid. Cell cycle analysis revealed comparable durations of each phase of the cell cycle in the Tat and control transfectants. Flow cytometric analysis using Hoechst 33342 and propidium iodide staining revealed that the Tat transfectants exhibited a higher percentage of apoptotic cells when compared to the control transfectants (29.1 +/- 3.1 vs. 11.43 +/- 3.1%). Incubation of Jurkat cells with recombinant HIV-1 Tat protein resulted in induction of apoptosis. The HIV-1 Tat protein induces apoptosis in a CD4-positive T cell line. Tat-induced programmed cell death may contribute to the lymphocyte depletion seen in persons infected with HIV-1.
Maximizing the Potential of Bevacizumab in Cancer Treatment (2004)

Promising results have been obtained with bevacizumab (Avestin; Genentech, Inc.; South San Francisco, CA) in clinical trials in patients with a range of solid tumors; however, to maximize the potential of this agent, further research is needed to clarify a number of important issues. These include the optimization of bevacizumab dosage and schedule of administration, the potential value of this agent in combination with other treatment modalities like chemotherapy and radiation, the management of toxicities, and the selection of patients most likely to benefit from treatment. Intriguing results from two recent phase III trials highlight the need for a better understanding of the best ways to incorporate bevacizumab into clinical practice. Ultimately, maximizing the potential value of this agent may require a more thorough understanding of bevacizumab's mechanism of action and the pathways mediating resistance.
Antitumor activity of berberrubine derivatives. (1976)

The antitumor activity of berberine, berberrubine, and their derivatives against sarcoma-180 ascites was determined by the total packed cell volume method. Berbine and tetrahydroberberine derivatives had no antitumor activity, but berberrubine (9-demethylberberine) and the ester derivatives of berberrubine had a strong antitumor activity. ED90 of berberrubine, its acetate and benzoate, were 15, 23, and 44 mg/kg, respectively. The therapeutic indices (LD10/ED90 by the present method) of these compounds were as follows: Berberrubine hydrochloride, 6.7 approximately 9.4; 9-acetyl-9-demethylberberine (9-acetylberberrubine) chloride, 7.6 approximately 8.7; 9-benzoyl-9-demethylberberine (9-benzoylberberrubine) chloride, 3.4 approximately 4.9.
Degradation of carboxy-terminal-tagged cytoplasmic proteins by the Escherichia coli protease HflB (FtsH) (1998)

Proteins with short nonpolar carboxyl termini are unstable in Escherichia coli. This proteolytic pathway is used to dispose of polypeptides synthesized from truncated mRNA molecules. Such proteins are tagged with an 11-amino-acid nonpolar destabilizing tail via a mechanism involving the 10Sa (SsrA) stable RNA and then degraded. We show here that the ATP-dependent zinc protease HflB (FtsH) is involved in the degradation of four unstable derivatives of the amino-terminal domain of the lambdacI repressor: three with nonpolar pentapeptide tails (cI104, cI105, cI108) and one with the SsrA tag (cI-SsrA). cI105 and cI-SsrA are also degraded by the ClpP-dependent proteases. Loss of ClpP can be compensated for by overproducing HflB. In an in vitro system, cI108 and cI-SsrA are degraded by HflB in an energy-dependent reaction, indicating that HflB itself recognizes the carboxyl terminus. These results establish a tail-specific pathway for removing abnormal cytoplasmic proteins via the HflB and Clp proteases.
Oxidation of wool: Alkali-solubility test for determining the extent of oxidation (1936)

Oxidizing agents attack the disulfide groups of the cystine in wool and increase the solubility of the wool in alkaline solutions. The determination of the alkalisolubility may be used as a measure of the extent to which the wool is oxidized. The method is applicaule as a control in practical processes, such as bleaching and chlorination, and offers a measure of the extent to which wool is degraded by photochemica l reactions. Data are presented which indicate a relationship between the chemical and physical degradation of wool fibers.
The GAD-given Right of Dentate Gyrus Granule Cells to Become GABAergic (2002)

JANUS, THE ANCIENT ROMAN GOD OF GATES AND DOORS HAD TWO FACES: one looked into the past, and the other, into the future. Do neurons possess a Janus face when it comes to neurotransmitters, or a given neuron is to be forever solely gamma-aminobutyric acid (GABA) ergic, glutamatergic, dopaminergic, peptidergic, or YOURPREFERREDTRANSMITTERergic? The answer is that the terminals of many neurons are homes to even more than two neurotransmitters. All this in spite of the "one neuron-one transmitter" usual misinterpretation of Sir Henry Hallett Dale's postulate, originally meant to indicate that a metabolic process taking place in the cell body can influence all processes of the same neuron. A large variety of neurons in the CNS, many of them GABAergic, produce and release chemicals that satisfy some of the criteria used to define neurotransmitters. The usual scenario for a dual-transmitter terminal is that the fast-acting transmitter such as GABA or glutamate is stored in regular synaptic vesicles, whereas a neuropeptide is stored in dense core vesicles (1). The vesicular zinc found in many glutamatergic terminals also may be considered to be a second neurotransmitter, based on its vesicular packaging with the aid of a specific vesicular transporter, and its postsynaptic actions through high-affinity binding sites and permeation through certain channels (2). Whenever a "fast" and a "slow" neurotransmitter are present in the same presynaptic terminal, it is customary to assume that their release can be differentially regulated (1). There is little convincing experimental support for this phenomenon in the mammalian CNS. The coexistence of two "fast" neurotransmitters in the same terminal is less frequent, but not unheard of. In neonatal sympathetic neurons cocultured with cardiac myocytes, norepinephrine and acetylcholine coexist and have opposite actions on the cardiac muscle cells (3). Very recently we learned that brain-derived neurotrophic factor acting at the low-affinity neurotrophin receptor p75(NTR), perhaps as part of a programmed developmental switch, can convert the phenotype of the sympathetic neuron from noradrenergic to cholinergic (4). Other examples of two fast neurotransmitters released from the same neuron include GABA and glycine in interneurons of the spinal cord (5) and glutamate and dopamine in ventral midbrain dopamine neurons (6). Of all CNS neurons, the granule cells of the dentate gyrus appear to be the champions of neurotransmitter colocalization: glutamate, enkephalin, dynorphin, zinc, and finally GABA (2)(7)(8)(9). With this many transmitters in a single neuron, there are probably different ways in which they can be released. Dynorphin and other opioid peptides can be released directly from the dendrites to inhibit excitatory transmission (8). A similar mechanism may take place for GABA, as described in cortical GABAergic neurons (10).
Mapping epitopes and antigenicity by site-directed masking (2006)

Here we describe a method for mapping the binding of antibodies to the surface of a folded antigen. We first created a panel of mutant antigens (beta-lactamase) in which single surface-exposed residues were mutated to cysteine. We then chemically tethered the cysteine residues to a solid phase, thereby masking a surface patch centered on each cysteine residue and blocking the binding of antibodies to this region of the surface. By these means we mapped the epitopes of several mAbs directed to beta-lactamase. Furthermore, by depleting samples of polyclonal antisera to the masked antigens and measuring the binding of each depleted sample of antisera to unmasked antigen, we mapped the antigenicity of 23 different epitopes. After immunization of mice and rabbits with beta-lactamase in Freund's adjuvant, we found that the antisera reacted with both native and denatured antigen and that the antibody response was mainly directed to an exposed and flexible loop region of the native antigen. By contrast, after immunization in PBS, we found that the antisera reacted only weakly with denatured antigen and that the antibody response was more evenly distributed over the antigenic surface. We suggest that denatured antigen (created during emulsification in Freund's adjuvant) elicits antibodies that bind mainly to the flexible regions of the native protein and that this explains the correlation between antigenicity and backbone flexibility. Denaturation of antigen during vaccination or natural infections would therefore be expected to focus the antibody response to the flexible loops.
Activation of the Estrogen Receptor Contributes to the Progression of Pulmonary Lymphangioleiomyomatosis via Matrix Metalloproteinase-Induced Cell Invasiveness (2008)

The invasion and destruction of lung parenchyma in LAM is, at least partially, an estrogen-MMP-driven process, which has major implications for therapeutic interventions.
2-D Mechanically resonating fiberoptic scanning display system (2010)

A micro-display system based on optical fiber driven by a 2-D piezoelectric actuator is presented. An optical fiber is extended from the free end of a 2-D piezoelectric actuator (free length: 4.3mm). A field programmable gate array (FPGA) drives the actuator using a triangular waveform to deflect the optical fiber in orthogonal directions. The FPGA also controls a LED light source and the light is coupled into a chemically tapered SMF-28 fiber (core diameter: 10μm). At a pre-set pairing of ne ar-resonance frequencies (Horizontal: 22Hz; Vertical:5070Hz), the deflected optical fiber in combination with controlled light pr oduces an output image with an approximate dimension of 0.3 × 0.3 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , and a potential resolution of 400 lines per scan. This pa per details the design and fabrication of the micro-display system. The mechanical and optical design for the microresonating scanner will be discussed. In addition, the mechanical and optical performance and the resulting output of the 2-D scanner will be presented.
The Role of PTF1-P48 in Pancreatic Acinar Gene Expression (2001)

The 100-base pair ELA1 transcriptional enhancer drives high level transcription to pancreatic acinar cells of transgenic mice and in transfected pancreatic acinar cells in culture. The A element within the enhancer is the sole positively acting element for acinar specificity. We show that the acinar cell-specific bHLH protein PTF1-P48 and the common bHLH cofactor HEB are part of the PTF1 complex that binds the A element and mediates its activity. Acinar-like activity of the enhancer can be reconstituted in HeLa cells by the introduction of P48, HEB, and the PDX1-containing trimeric homeodomain complex that binds the second pancreatic element of the enhancer. The 5' region of the mouse Ptf1-p48 gene from -12.5 to +0.2 kilobase pairs contains the regulatory information to direct expression in transgenic mice to the pancreas and other organs of the gut that express the endogenous Ptf1-p48 gene. The 5'-flanking sequence contains two activating regions, one of which is specific for acinar cells, and a repressing domain active in non-pancreatic cells. Comparison of the 5'-gene flanking regions of the mouse, rat, and human genes identified conserved sequence blocks containing binding sites for known gut transcription factors within the acinar cell-specific control region.
Should Regulators Reveal Information About Banks (2014)

Regulators collect and produce information about banks. This information helps regulators monitor the safety and soundness of the banking system, and it also helps policymakers preserve financial stability. A key issue is whether this information should be made public and, if so, to what extent. In this article, we will explore some of the tradeoffs involved.
Cell-type specificity of interferon-gamma-mediated HLA class I gene transcription in human hematopoietic tumor cells (1991)

Major histocompatibility complex class I gene expression plays a central role in cellular immunity and tumor surveillance. A substantial proportion of spontaneous tumors are class I-deficient and numerous experiments have suggested that alterations in class I expression may alter oncogenicity and, as a result, have potential therapeutic impact. Interferons (IFNs) are able to upregulate class I expression by mechanisms that remain to be elucidated, but which appear to be IFN- and cell-type specific. We have characterized in detail the in vivo class I transcriptional response to IFN-gamma in two human hematopoietic tumor cell lines, the class I-deficient K562 cell line and the class I-positive Ramos cell line. In each, IFN-gamma induces a rapid increase in class I transcription, which is sustained in Ramos cells, but transient in K562 cells. In each, stimulation by IFN-gamma is dependent on ongoing protein synthesis, suggesting the requirement for production of a “primary response” protein. These data suggest that more than one type of IFN-gamma-induced signal is operative in the transcriptional response to IFN-gamma. Cycloheximide alone is also capable of inducing a rapid increase in class I transcription in both cell types, suggesting that constitutive attenuation of class I transcription may be a common phenomenon, and that IFN-gamma may act, in part, by interfering with such attenuation.
T Cell Receptor–initiated Calcium Release Is Uncoupled from Capacitative Calcium Entry in Itk-deficient T Cells (1998)

Itk, a Tec family tyrosine kinase, plays an important but as yet undefined role in T cell receptor (TCR) signaling. Here we show that T cells from Itk-deficient mice have a TCR-proximal signaling defect, resulting in defective interleukin 2 secretion. Upon TCR stimulation, Itk-/- T cells release normal amounts of calcium from intracellular stores, but fail to open plasma membrane calcium channels. Since thapsigargin-induced store depletion triggers normal calcium entry in Itk-/- T cells, an impaired biochemical link between store depletion and channel opening is unlikely to be responsible for this defect. Biochemical studies indicate that TCR-induced inositol 1,4,5 tris-phosphate (IP3) generation and phospholipase C gamma1 tyrosine phosphorylation are substantially reduced in Itk-/- T cells. In contrast, TCR-zeta and ZAP-70 are phosphorylated normally, suggesting that Itk functions downstream of, or in parallel to, ZAP-70 to facilitate TCR-induced IP3 production. These findings support a model in which quantitative differences in cytosolic IP3 trigger distinct responses, and in which only high concentrations of IP3 trigger the influx of extracellular calcium.