gebhart/patrepeval huggingface dataset:
Desaturation and Hydroxylation (2002)

Exchanging the identity of amino acids at four key locations within the Arabidopsis thaliana oleate desaturase (FAD2) and the Lesquerella fendleri hydroxylase/desaturase (LFAH) was shown to influence partitioning between desaturation and hydroxylation (Broun, P., Shanklin, J., Whittle, E., and Somerville, C. (1998) Science 282, 1315-1317). We report that four analogous substitutions in the FAD2 sequence by their equivalents from the castor oleate hydroxylase result in hydroxy fatty acid accumulation in A. thaliana to the same levels as for the wild-type castor hydroxylase. We also describe the relative contribution of these substitutions, both individually and in combination, by analyzing the products resulting from their expression in A. thaliana and/or Saccharomyces cerevisiae. Yeast expression showed that M324V, a change reachable by a single point mutation, altered the product distribution approximately 49-fold, and that residue 148 is also a predominant determinant of reaction outcome. Comparison of residues at position 148 of FAD2, LFAH, and the Ricinus oleate hydroxylase prompted us to rationally engineer LFAH-N149I, a variant with approximately 1.9-fold increase in hydroxylation specificity compared with that of wild-type LFAH. Control experiments showed that the wild-type Arabidopsis thaliana FAD2 desaturase has inherent, low level, hydroxylation activity. Further, fatty acid desaturases from different kingdoms and with different regiospecificities exhibit similar intrinsic hydroxylase activity, underscoring fundamental mechanistic similarities between desaturation and hydroxylation. For LFAH mutants the hydroxylation:desaturation ratio is 5-9-fold higher for 18-carbon versus 16-carbon substrates, supporting our hypothesis that substrate positioning in the active site plays a key role in the partitioning of catalytic specificity.
Atomic Structure of theGaAs(001)−(2×4)Surface Resolved Using Scanning Tunneling Microscopy and First-Principles Theory (1999)

The atomic arrangement of the technologically important As-rich $\mathrm{GaAs}(001)\ensuremath{-}(2\ifmmode\times\else\texttimes\fi{}4)$ reconstructed surface is determined using bias-dependent scanning tunneling microscopy (STM) and first-principles electronic structure calculations. The STM images reveal the relative position and depth of the atomic-scale features within the trenches between the top-layer As dimers, which are in agreement with the $\ensuremath{\beta}2(2\ifmmode\times\else\texttimes\fi{}4)$ structural model. The bias-dependent simulated STM images reveal that a retraction of the topmost dangling bond orbitals is the novel electronic mechanism that enables the STM tip to image the trench structure.
ChemInform Abstract: SYNTHESIS AND BIOLOGICAL ACTIVITY OF NEW β‐LACTAM AND THIAZOLIDINONES CONTAINING A SULFANILAMIDE MOIETY (1982)

Abstract Aus den Sulfonamiden (I) und den aromatischen Aldehyden (II) werden die Schiffschen Basen (III) erhalten, aus denen mit Chloracetyl‐ Chlorid (IV) und Triethylamin die Azetidinone (V) und mit Thioglykolsäure (VI) die Thiazolidinone (VII) hergestellt werden.
The Biology of hyaluronan (1989)

Partial table of contents: Secondary Structures in Hyaluronan Solutions: Chemical and Biological Implications (J. Scott). Turnover and Metabolism of Hyaluronan (J. Fraser & T. Laurent). Enzymic Pathways of Hyaluronan Catabolism (L. Rod?n, et al.). Hyaluronan and Hyaluronan-Binding Proteins in Cartilaginous Tissues (R. Mason, et al.). The Role of a Cell-Associated Hyaluronan-Binding Protein in Fibroblast Behavior (E. Turley). The Role and Regulation of Tumor-Associated Hyaluronan (W. Knudson, et al.). Interactions Between Cells of the Immune System and Hyaluronate Synthesis by Human Dermal Fibroblasts (T. Whiteside & R. Buckingham). Hyaluronan and Angiogenesis (D. West & S. Kumar). Changes in Hyaluronan Concentration in Tissues and Body Fluids in Disease States (A. Engstr?m-Laurent). The Specific Interaction Between Fibrin(ogen) and Hyaluronan: Possible Consequences in Hemostasis, Inflammation and Wound Healing (P. Weigel, et al.). General Discussion. Index of Contributors. Subject Index.
The 5′-HS4 chicken β-globin insulator is a CTCF-dependent nuclear matrix-associated element (2004)

The protein CTCF plays an essential role in the action of a widely distributed class of vertebrate enhancer-blocking insulators, of which the first example was found in a DNA sequence element, HS4, at the 5' end of the chicken beta-globin locus. HS4 contains a binding site for CTCF that is necessary and sufficient for insulator action. Purification of CTCF has revealed that it interacts with proteins involved in subnuclear architecture, notably nucleophosmin, a 38-kDa nucleolar phosphoprotein that is concentrated in nuclear matrix preparations. In this report we show that both CTCF and the HS4 insulator element are incorporated in the matrix; HS4 incorporation depends on the presence of an intact CTCF-binding site. However the DNA sequence in the neighborhood of HS4 is not like that of canonical matrix attachment regions, and its incorporation into the matrix fraction is not sensitive to ribonuclease, suggesting that the insulator is a distinct matrix-associated element.
Synergistic effects of purified recombinant human and murine B cell growth factor-1/IL-4 on colony formation in vitro by hematopoietic progenitor cells. Multiple actions. (1988)

Purified recombinant human B cell growth factor-1/IL-4 was evaluated, alone and in combination, with purified preparations of recombinant human (rhu) CSF or erythropoietin (Epo) for effects on colony formation by human bone marrow CFU-GM progenitor cells (GM) and burst forming unit-E progenitor cells. rhu IL-4 synergized with rhu G-CSF to enhance granulocyte colony formation, but had no effect on CFU-GM colony formation stimulated by rhu GM-CSF, rhu IL-3, or rhu CSF-1. Rhu IL-4 synergized with Epo to enhance BFU-E colony formation equal to that of Epo plus either rhu IL-3, rhu GM-CSF, or rhu G-CSF. Removal of adherent cells and T lymphocytes did not influence the synergistic activities of rhu IL-4. Rmu IL-4, synergized with rhu G-CSF, but not with rmu GM-CSF, rmu IL-3, or natural mu CSF-1, to enhance CFU-GM (mainly granulocyte) colony numbers by a greater than 90% pure preparation of murine CFU-GM. Also, rhu IL-4 at low concentrations enhanced release of CSF and at higher concentrations the release also of suppressor molecules from human monocytes and PHA-stimulated human T lymphocytes. Use of specific CSF antibodies suggested that rhu IL-4 was enhancing the release of G-CSF and CSF-1 from monocytes and the release of GM-CSF and possibly G-CSF from PHA-stimulated T lymphocytes. Use of antibodies for TNF-alpha, IFN-gamma, or TNF-beta as well as measurement of TNF and IFN titers suggested that the suppressor molecule(s) released from monocytes were acting with TNF-alpha and those released from PHA-stimulated T lymphocytes were acting with IFN-gamma. These results implicate B cell growth factor-1/IL-4 as a synergistic activity for hematopoietic progenitors and suggest that the actions can be on both progenitor and accessory cells.
New drugs in prostate cancer (2016)

The standard primary treatment for advanced prostate cancer has been hormonal therapy since the 1940s. However, prostate cancer inevitably progresses to castration-resistant prostate cancer (CRPC) after a median duration of 18 months of androgen deprivation therapy. In patients with CRPC, docetaxel has been regarded as the standard treatment. However, survival advantages of docetaxel over other treatments are slim, and the need for new agents persists. In recent years, novel agents, including abiraterone, enzalutamide, cabazitaxel, radium-223, and sipuleucel-T, have been approved for the treatment of CRPC, and more such agents based on diverse mechanisms are under investigation or evaluation. In this article, the authors reviewed the current literature on recent advances in medical treatment of prostate cancer, especially CRPC. In addition, the authors elaborated on novel drugs for prostate cancer currently undergoing investigation and their mechanisms.
Antibody engineering and its applications in tumor targeting and intracellular immunization (2000)

During the last decade, recombinant antibody engineering has emerged as one of the most promising approaches for the design, selection and production of molecules for basic research, medicine and the pharmaceutical industry. This MiniReview describes the major findings that have led to the development of this powerful technique, with an emphasis on the use of Escherichia coli and filamentous phage as a tool allowing powerful selection procedures from large libraries as well as the use of intracellular expression of antibody fragments as a new class of neutralizing molecules with a potential use in therapy. The future of these rapidly evolving technologies is discussed.
Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. (1993)

Although patients with thromboembolic disease frequently have family histories of thrombosis, well-defined defects such as inherited deficiencies of anticoagulant proteins are found only in a minority of cases. Based on the hypothesis that a poor anticoagulant response to activated protein C (APC) would predispose to thrombosis, a set of new coagulation assays was developed that measure the anticoagulant response in plasma to APC. A middle-aged man with a history of multiple thrombotic events was identified. The addition of APC to his plasma did not result in a normal anticoagulant response as measured by prolongation of clotting time in an activated partial thromboplastin time (APTT) assay. Four of the proband's relatives had medical histories of multiple thrombotic events, and they and several other family members responded poorly to APC in the APTT-based assay. Subnormal anticoagulant responses to APC were also found in factor IXa- and Xa-based assays. Several possible mechanisms for the observed phenomenon were ruled out, such as functional protein S deficiency, a protein C-inhibitory antibody, or a fast-acting protease inhibitor against APC. Moreover, restriction fragment-length polymorphism analysis excluded possible linkage of the underlying molecular defect to factor VIII and von Willebrand factor genes. We now describe a previously unrecognized mechanism for familial thromboembolic disease that is characterized by poor anticoagulant response to APC. This would appear to be explained best by a hypothesized inherited deficiency of a previously unrecognized cofactor to APC. As we have identified two additional, unrelated cases with thrombosis and inherited poor anticoagulant response to APC, this may constitute an important cause for familial thrombophilia.
Fundamental limits to imaging resolution for focused ion beams (1996)

This article investigates the limitations on the formation of focused ion beam images from secondary electrons. We use the notion of the information content of an image to account for the effects of resolution, contrast, and signal-to-noise ratio and show that there is a competition between the rate at which small features are sputtered away by the primary beam and the rate of collection of secondary electrons. We find that for small features, sputtering is the limit to imaging resolution, and that for extended small features (e.g., layered structures), rearrangement, redeposition, and differential sputtering rates may limit the resolution in some cases.
Arterial thrombus formation (2010)

Platelet and coagulation factor-dependent thrombus formation is critical to limit posttraumatic blood loss at sites of vascular injury. However, under pathological conditions like rupture of an atherosclerotic plaque, it may also lead to vessel occlusion causing myocardial infarction or stroke. Therefore, antithrombotic treatment is the prime therapeutic option in the prophylaxis and treatment of ischaemic cardio- and cerebrovascular diseases. The use of existing antithrombotic agents is, however, limited by their inherent effect on primary haemostasis. In recent years, major advances have been made in understanding the mechanisms of thrombus formation in haemostasis and thrombosis and some studies raised the interesting possibility that occlusive thrombus formation and haemostasis may involve partially different mechanisms. This review briefly summarizes these developments and highlights newly identified mechanisms involved in platelet adhesion and activation, intracellular calcium signaling, integrin activation and initiation of coagulation. The suitability of these pathways as novel targets for antithrombotic therapy is discussed.
Critical tasks in high aspect ratio silicon dry etching for microelectromechanical systems (2003)

The process of pattern transfer of desired topological features into silicon plays a critical role for the production of microelectronic and photonic devices, and micro- and nanoelectromechanical systems. Any deviation from the desired shape of the pattern limits density, yield, and reliability of these devices. Gas reactivity, pressure, ion, electron, and reactant transport to the surface, and product transport away from the surface, have all been identified as important issues that control the microscopic uniformity in high aspect ratio etching. When etch-inhibiting chemistry by the gas chopping deep reactive ion etching (RIE) was employed, it caused enormous complications in the scaling of etching rates, with increasing aspect ratio. Using an energy-resolving quadrupole mass spectrometer assembled into the cathode, specially designed test features, and etching simulation models, we establish the link between etch process parameters such as pressure, rf power, etching gas chemistry, temperature, and the physical and chemical process parameters like energy and angular distribution of ions and neutrals, radical sticking, and surface charging. The most significant effects like RIE lag, notching, bowing, faceting, microtrenching, profile shape dependence, etc. will be discussed in this article. 2003 American Vacuum Society.
Erosion of poly(anhydride-co-imides): A preliminary mechanistic study (1996)

A new class of biodegradable polymers that show promising characteristics for orthopedic applications was investigated. This study examines aspects underlying the polymer erosion of poly[trimellitylimidoglycine-co-1,6-bis(carboxyphenoxy)hexane] and poly[pyromellitylimidoalanine-co-1,6-bis(carboxyphenoxy)hexane].Copolymer degradation was studied by examining the anhydride bond hydrolysis and copolymer composition by IR and NMR spectroscopy. Hydrolysis of the anhydride bonds occurred much faster than did the dissolution of the hydrolyzed products, leading to the formation of two distinct erosion zones. The two erosion zones were observed by light and scanning electron microscopy with erosion originating at the surface and moving to the center of the polymer samples. © 1996 John Wiley & Sons, Inc.
Anaphylactoid Reactions Associated with Parenteral Cyclosporine Use: Possible Role of Cremophor EL (1985)

Acute anaphylactoid reactions occurred immediately after initiation of intravenous infusions of cyclosporine in three patients post-organ transplantation. Shortness of breath, flushing, tachypnea, chest pain, pruritus, or urticaria were noted; rapid recovery followed cessation of drug infusion. Subsequently, oral cyclosporine has been used in each patient without recurrence of the observed reaction. The presence of Cremophor EL as an emulsifying agent in the parenteral dosage formulation of cyclosporine is a likely etiology for this acute adverse reaction. Slowed rates of drug infusion and antihistamine premedication may permit continued intravenous cyclosporine use in affected patients.
PHYTOCHEMICAL INVESTIGATION OF CERTAINCESTRUMSPECIES (1971)

A phytochemical screening of Cestrum species C. aurantiacum, C. diurnum and C. purpureum was carried out revealing the presence of steroidal saponins, sterols, catechol tannins, carbohydrates and flavonoids. Steroidal alkaloids are found only in C. purpureum.
Early persistent activation of sperm K+ channels by the egg peptide speract. (1992)

Transduction by sperm of the instructive signal provided by the egg peptide speract involves rapid, complex changes in internal ion and cyclic nucleotide content. Here, investigations of hypotonically swollen sperm provide insight into the underlying processes and identify K+ channel activation as an initial ionic event in gamete recognition. A sustained hyperpolarization of swollen sperm is promoted by less than 2.5 pM speract and is followed (with greater than 100 pM speract) by transient repolarization and (with greater than 10 nM speract) by depolarization that is dependent on external Ca2+. Monophasic increases in pHi are produced only by greater than 25 pM speract, indicating that hyperpolarization may not directly promote alkalinization. Increased K(+)-selective (K+ greater than Rb+ greater than Cs+ greater than Na+) membrane permeability is found after all speract greater than 2.5 pM, suggesting that hyperpolarization results from persistent activation of K+ channels and that repolarization has a different ionic basis. Supporting this contention, the K+ channel blocker tetraethylammonium (20 mM) inhibits the increased K+ permeability that follows treatment of swollen sperm (and of sperm in seawater) with 2.5 pM speract. Such induced activation of K+ channels is observed in patch-clamped swollen sperm examined in the cell-attached configuration, upon application of 5-50 pM speract to the bath medium. The efficacy of externally applied speract and its potency indicate that activation is indirect and probably involves an as yet unidentified diffusible mediator whose production is promoted by speract at concentrations 0.01-0.001 times those predicted from reported estimates of the Kd for the known speract receptor.
Efficacy of Octreotide Acetate in Treatment of Severe Postgastrectomy Dumping Syndrome (1990)

The present study evaluates the acute and chronic use of a long-acting somatostatin analog, octreotide acetate, in the treatment of patients with severe postgastrectomy dumping syndrome. In the acute phase, 10 patients with severe dumping were studied over 2 consecutive days before and for 3 hours after the ingestion of a 'dumping breakfast' in a randomized double-blind fashion. On one day octreotide (100 micrograms) was given subcutaneously 30 minutes before the test meal and on the other day an equal volume of vehicle was injected. An additional group of six postgastrectomy patients without dumping were studied in a similar fashion and these acted as controls. During placebo treatment the test meal resulted in an immediate increase (p less than 0.01) in the pulse rate and in plasma levels of glucose, glucagon, pancreatic polypeptide, neurotensin, and insulin. Similar changes were seen in the control group with respect to placebo; however glucagon and neurotensin (p less than 0.05) did not show the same magnitude of increase as seen with placebo. Treatment with octreotide acetate prevented the development of both vasomotor and gastrointestinal symptoms and completely ablated all of the above responses in plasma peptides. These changes were associated with complete ablation of diarrhea (p less than 0.001). Pretreatment with octreotide acetate completely suppressed the rise in plasma insulin response to the meal and this ablated the late hypoglycemia of dumping. Treatment with octreotide acetate resulted in delayed gastric emptying and transit time (578 +/- 244 minutes) versus 76 +/- 23 minutes with placebo and 125 +/- 36 minutes in controls (p less than 0.05). Chronic daily treatment with octreotide acetate resulted in minimal side effects. These patients demonstrated a stable fasting plasma glucose, normal liver function tests, and an average weight gain of 11% during a 12-month period. In addition most patients were able to resume employment. The long-acting somatostatin analog, octreotide acetate, is highly effective in preventing the development of symptoms of severe dumping syndrome, both vasomotor and gastrointestinal.
The object-oriented structured design notation for software design representation (1990)

The development of a notation that supports key software structure concepts and design principles, is discussed. The notation should let designers represent modules, interfaces, hidden information, concurrency, message passing, invocation of operations and overall program structure in a comprehensive way. The authors examine three categories of approach to architectural design: object-oriented design, functional decomposition, and data structure design. They present their design notation, called object-oriented structured design (OOSD) which achieves the above-stated goal. They discuss classes in OOSD, its handling of asynchronous processes, and its design methods and rules. Automated support for OOSD is considered.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Glycan‐dependent signaling: O‐linked N‐acetylglucosamine (2001)

The addition of O-linked N-acetylglucosamine (O-GlcNAc) to target proteins may serve as a signaling modification analogous to protein phosphorylation. Like phosphorylation, O-GlcNAc is a dynamic modification occurring in the nucleus and cytoplasm. Various analytical methods have been developed to detect O-GlcNAc and distinguish it from glycosylation in the endomembrane system. Many target molecules have been identified; these targets are typically components of supramolecular complexes such as transcription factors, nuclear pore proteins, or cytoskeletal components. The enzymes responsible for O-GlcNAc addition and removal are highly conserved molecules having molecular features consistent with a signaling role. The O-GlcNAc transferase and O-GlcNAcase are likely to act in consort with kinases and phosphatases generating various isoforms of physiological substrates. These isoforms may differ in such properties as protein-protein interactions, protein stability, and enzymatic activity. Since O-GlcNAc plays a critical role in the regulation of signaling pathways of higher plants, the glycan modification is likely to perform similar signaling functions in mammalian cells. Glucose and amino acid metabolism generates hexosamine precursors that may be key regulators of a nutrient sensing pathway involving O-GlcNAc signaling. Altered O-linked GlcNAc metabolism may also occur in human diseases including neurodegenerative disorders, diabetes mellitus and cancer.
A CSR-NL interface specification version 1.5 (1989)

Spoken Language Systems will require integration of continuous speech recognition and natural language processing. This is a proposed specification for an interface between a continuous speech recognizer (CSR) and a natural language processor (NLP) to form a spoken language system. Both components are integrated with a stack controller and contribute to the search control. The specification also defines a "Top-N" mode in which a "first part" outputs a list of top N scored sentences for postprocessing by a "second part". An additional use for this specification might be NLP evaluation testing: a common simulated CSR could be interfaced to each site's NLP to provide identical testing environments.