gebhart/patrepeval huggingface dataset:
Structure activity relationships of synthetic antibiotic analogues of chryscandin. (1985)

Anti-yeast activity with a series of chryscandin derivatives showed that the O-methyl-L-tyrosyl moiety is not always required for activity at the target site. On the other hand, the adenyl-3'-aminoribofuranuronic acid moiety seems to be essential for biological activity. Therefore, the various acyl derivatives on the amino group of the sugar part of the nucleoside were synthesized. 1-(6-Amino-9H-purin-9-yl)-3-(S-benzyl-L-cysteinylamino)- 1,3-dideoxy-beta-D-ribofuranuronic acid (16) showed the highest efficacy among them against Candida albicans. It exhibited sixteen-fold enhanced activity in vitro compared with that of native chryscandin. The in vivo activity of 16 against experimental infection of C. albicans showed the almost same as that of 5-fluorocytosine and a superior to that of ketoconazole.
Terabit-per-square-inch data storage with the atomic force microscope (1999)

An areal density of 1.6 Tbits/in.2 has been achieved by anodically oxidizing titanium with the atomic force microscope (AFM). This density was made possible by (1) single-wall carbon nanotubes selectively grown on an AFM cantilever, (2) atomically flat titanium surfaces on α-Al2O3 (1012), and (3) atomic scale force and position control with the tapping-mode AFM. By combining these elements, 8 nm bits on 20 nm pitch are written at a rate of 5 kbit/s at room temperature in air.
Access control for the SPIN extensible operating system (1997)

Summary form only given. In the SPIN operating system (B.N. Bershad et al., 1995; Przemyslaw Pardyak and B.N. Bershad, 1996) built at the University of Washington, we are experimenting with a version of domain and type enforcement (DTE) (L. Badger et al., 1995) that has been extended to address the security concerns of extensible systems. The SPIN operating system defines an extension infrastructure, together with a core set of extensible services, that allows for the fine grained and safe composition of extensions within the operating system kernel. Extensions are written in Modula-3, a type-safe programming language, and execute within the same address space. They interact by calling other parts of the system and by extending existing interfaces to provide new services. A central event dispatcher supports both mechanisms: to call on a service, an extension raises an event, and, to extend an existing interface, an extension registers a handler for that event. The invocation mechanism for events is simply a procedure call, and no context switches are required for the interaction between subsystems (since all extensions are co-located in the same address space).
Effect of Different Carbon Sources on the Production of Succinic Acid Using Metabolically Engineered Escherichia coli (2007)

Succinic acid (SA) is an important platform molecule in the synthesis of a number of commodity and specialty chemicals. In the present work, dual-phase batch fermentations with the E. coli strain AFP184 were performed using a medium suited for large-scale industrial production of SA. The ability of the strain to ferment different sugars was investigated. The sugars studied were sucrose, glucose, fructose, xylose, and equal mixtures of glucose and fructose and glucose and xylose at a total initial sugar concentration of 100 g L-1. AFP184 was able to utilize all sugars and sugar combinations except sucrose for biomass generation and succinate production. For sucrose as a substrate no succinic acid was produced and none of the sucrose was metabolized. The succinic acid yield from glucose (0.83 g succinic acid per gram glucose consumed anaerobically) was higher than the yield from fructose (0.66 g g-1). When using xylose as a carbon source, a yield of 0.50 g g-1 was obtained. In the mixed-sugar fermentations no catabolite repression was detected. Mixtures of glucose and xylose resulted in higher yields (0.60 g g-1) than use of xylose alone. Fermenting glucose mixed with fructose gave a lower yield (0.58 g g-1) than fructose used as the sole carbon source. The reason is an increased pyruvate production. The pyruvate concentration decreased later in the fermentation. Final succinic acid concentrations were in the range of 25-40 g L-1. Acetic and pyruvic acid were the only other products detected and accumulated to concentrations of 2.7-6.7 and 0-2.7 g L-1. Production of succinic acid decreased when organic acid concentrations reached approximately 30 g L-1. This study demonstrates that E. coli strain AFP184 is able to produce succinic acid in a low cost medium from a variety of sugars with only small amounts of byproducts formed.
Identification of patient subsets among those presumptively diagnosed with, referred, and/or followed up for systemic lupus erythematosus at a large tertiary care center (1995)

When the ACR criteria for SLE are used to determine eligibility for lupus studies, a group of patients with clinically unequivocal SLE are excluded. A group of patients with fibromyalgia-like manifestations, who test positive for ANA and differ clinically and sociodemographically from the patients in the other 2 groups, very likely do not belong within the spectrum of SLE.
Improved intrinsic dynamic distortions in directly modulated semiconductor lasers by optical injection locking (1999)

The effects of optical injection locking on the nonlinear distortions of directly modulated semiconductor distributed feedback (DFB) lasers are investigated experimentally. The second harmonic distortion (SHD) and third harmonic distortion (THD), as well as the third-order intermodulation distortion (IMD3), are measured as functions of modulation frequency for both the free-running and injection-locked lasers. Under strong injection locking with -8-dB injection ratio, the SHD and THD of the DFB laser have been suppressed by 15 dB from 2 to 4 GHz. Moreover, nearly 15-dB reduction in IMD3 has been observed from 1.4 to 3.0 GHz with the same injection conditions. We also found that the injection locking is not effective in reducing the low-frequency distortions.
Rapid, Nonmechanical, Damage-Free Figuring Of Optical Surfaces Using Plasma-Assisted Chemical Etching (PACE): Part I Experimental Results (1989)

We present experimental results of an ongoing investigation demonstrating that Plasma Assisted Chemical Etching (PACE) can rapidly and controllably figure and smooth optical surfaces without mechanical contact; thus, removing the constraints on the design of optical elements imposed by mechanical processes, and, allowing higher quality optical surfaces. This process employs a plasma etch process originally developed to pattern micro-electronic circuits by etching through a relatively non-erodable lithographically patterned mask. The PACE process shapes the optical surface by removing material in a small area under a confined reactive gas plasma moved over the surface. Rates of removal as high as 10 m per minute are obtainable with accurate control. The removal footprint can be varied during the process. PACE inherently smooths or polishes while removing material, exposing a virgin surface free of process generated contamination and subsurface damage. Although other materials can also be figured by a PACE process, for this study, apparatus and processes were developed to explore the figuring of fused silica. Results will be shown demonstrating: repeatability and control of removal rate and footprint; predictability of material removal with plasma &quot;tool&quot; motion; and smoothing.
Prostaglandins, Platelets, And Atherosclerosi (1980)

Metabolism of arachidonic acid (AA) in blood platelets and in vascular endothelium does not lead to prostaglandins, but thromboxane A2 and prostacyclin are generated. These labile metabolites of AA antagonize each other: thromboxane A2 is a vasoconstrictor and proaggregatory agent, whereas prostacyclin dilates arteries, prevents platelets from aggregation, and dissipates the preformed platelet clumps. Prostacyclin is a powerful stimulator of adenylate cyclase in platelets and therefore its antiplatelet action is potentiated by phosphodiesterase inhibitors such as theophylline or dipyridamole. Cyclo-oxygenase of AA is inhibited by aspirin, thromboxane synthetase by analogues of prostaglandin endoperoxides, and prostacyclin synthetase by linear lipid peroxides. A hypothesis is put forward that atherosclerosis develops because of pathological, nonenzymic lipid peroxides. A hypothesis is put forward that atherosclerosis develops because of pathological, nonenzymic lipid peroxydation in the body and the subsequent molecular damage to prostacyclin synthetase in the rheologically determined areas of arterial walls. Endothelium deprived of prostacyclin is the basis for microthrombi formation, and follows a sequence of events described by Rokitansky and later by Ross. Prostacyclin is also a circulating hormone which is generated by the lungs. Thereby a damage of this "endocrine gland" by respiratory disorders, air pollution, or tobacco smoking are likely to contribute to pathogenesis of atherosclerosis, myocardial infarction, and arterial thromboembolism. Pharmacological treatment and prevention of these diseases should logically include antioxydants, prostacyclin and its analogues, thromboxane synthetase inhibitors and perhaps cyclooxygenase inhibitors (aspirin ?). Prostacyclin was already infused intravenously to men and its powerful antiaggregatory and deaggregatory actions were demonstrated. These properties of prostacyclin along with its vasodilator and positive inotropic actions destine this hormone to be a new type of antithrombotic drug in acute myocardial infarction.
Toll-like receptors in cardiovascular diseases (2003)

The Toll-like receptor family recognizes mostly exogenous ligands like bacterial lipopolysaccharides or DNA and activates the inflammatory cell. Evidence is accumulating that these Toll-like receptors are important in cardiovascular pathologies. Recently, expression of Toll-like receptors in arterial and myocardial cells has been shown and mouse knockout and human studies on polymorphisms point to a role of Toll-like receptor 4 in neointima formation and atherosclerosis. It is now becoming clear that these receptors not only serve as receptors for pathogen-associated molecular patterns but are also involved in the initiation and progression of cardiovascular pathologies.
A Web Service Enabling Gradable Post-edition of Pre-translations Produced by Existing Translation Tools: Practical Use to Provide Highquality Translation of an Online Encyclopedia (2009)

SECTra_w is a Web-based system offering several services, such as supporting MT evaluation campaigns and online post-editing of MT results, to produce reference transla-tions adapted to classical MT systems not built by machine learning from a parallel cor-pus. The service we are interested in here is the possibility for its users to import a docu-ment, or a set of documents (not only a list of preprocessed segments), and achieve high-quality translation by applying on-line human post-edition to results of Machine Translation systems. A community of contributing post-editors may carry out the on-line human post-edition. In this paper, we describe the use of SECTra_w to translate into French a set of 25 html documents (about 220,000 words) on water and ecology from the on-line Encyclo-pedia of Life Support Systems1 (EOLSS) us-ing a contributive on-line human post-edition framework. 1
Protein Flexibility and Species Specificity in Structure-Based Drug Discovery:  Dihydrofolate Reductase as a Test System (2007)

In structure-based drug discovery, researchers would like to identify all possible scaffolds for a given target. However, techniques that push the boundaries of chemical space could lead to many false positives or inhibitors that lack specificity for the target. Is it possible to broadly identify the appropriate chemical space for the inhibitors and yet maintain target specificity? To address this question, we have turned to dihydrofolate reductase (DHFR), a well-studied metabolic enzyme of pharmacological relevance. We have extended our multiple protein structure (MPS) method for receptor-based pharmacophore models to use multiple X-ray crystallographic structures. Models were created for DHFR from human and Pneumocystis carinii. These models incorporate a fair degree of protein flexibility and are highly selective for known DHFR inhibitors over drug-like non-inhibitors. Despite sharing a highly conserved active site, the pharmacophore models reflect subtle differences between the human and P. carinii forms, which identify species-specific, high-affinity inhibitors. We also use structures of DHFR from Candida albicans as a counter example. The available crystal structures show little flexibility, and the resulting models give poorer performance in identifying species-specific inhibitors. Therapeutic success for this system may depend on achieving species specificity between the related human host and these key fungal targets. The MPS technique is a promising advance for structure-based drug discovery for DHFR and other proteins of biomedical interest.
HIV Protease Inhibitors: Advances in Therapy and Adverse Reactions, Including Metabolic Complications (1999)

Protease inhibitors (PIs) effectively inhibit replication of the human immunodeficiency virus (HIV), and reduce mortality and prolong survival in patients with HIV infection. Newer PIs saquinavir (soft gelatin capsule) and amprenavir, as well as other PIs, may be effective when administered twice/day. Adverse reactions may occur, as well as metabolic complications and interactions between PIs and other drugs, including other PIs. The strategy of combining PIs is based on specific pharmacologic interactions among the agents.
Preincubation of human synovial cells with IL-1 modulates prostaglandin E2 release in response to bradykinin. (1989)

Kinins are vasoactive peptides whose potent inflammatory and bone resorbing properties suggest a role for these autacoids in the pathogenesis of inflammatory arthritis. We used cultured human synovial cells as a model to evaluate the effects of bradykinin on articular tissue. In resting synovial cells, bradykinin was a relatively ineffective stimulus for PGE2 production. However, after a period of preincubation with the cytokine, IL-1, which is itself a stimulus for PGE2 production, synovial cells exhibited a further striking time- and dose-dependent response to bradykinin. Maximal release of PGE2 was observed in response to 10(-7) to 10(-6) M bradykinin after first pretreating the cells for 24 h with 5 to 10 U/ml of IL-1. rIL-1 alpha and IL-1 beta, as well as rTNF-alpha, induced a similar response to bradykinin in synovial cells, whereas recombinant IL-2 did not. The bradykinin analog, lysylbradykinin, was equipotent in inducing PGE2 release from IL-1 pretreated synovial cells, whereas des(Arg9) bradykinin, substance P, and neurokinins A and B were ineffective in this regard in both IL-1-pretreated and in resting cells. Synovial cells derived from patients with rheumatoid arthritis and osteoarthritis responded similarly to bradykinin. The synergistic response in PGE2 production induced by IL-1 and bradykinin was significantly inhibited by pretreatment with 1 microM indomethacin or dexamethasone (96 and 94% inhibition, respectively). In addition, the response was abrogated by pretreatment with 10 micrograms/ml of cycloheximide or actinomycin D (81 and 97% inhibition, respectively). These data provide the first description of synergism of IL-1 with a noncytokine peptide in human synovial cells. The ability of IL-1 to increase the responsiveness of synovial tissues to bradykinin may play an important role in potentiating inflammatory responses within the joint.
Molecular basis for a link between complement and the vascular complications of diabetes (2000)

Activated terminal complement proteins C5b to C9 form the membrane attack complex (MAC) pore. Insertion of the MAC into endothelial cell membranes causes the release of growth factors that stimulate tissue growth and proliferation. The complement regulatory membrane protein CD59 restricts MAC formation. Because increased cell proliferation characterizes the major chronic vascular complications of human diabetes and because increased glucose levels in diabetes cause protein glycation and impairment of protein function, we investigated whether glycation could inhibit CD59. Glycation-inactivation of CD59 would cause increased MAC deposition and MAC-stimulated cell proliferation. Here, we report that (i) human CD59 is glycated in vivo, (ii) glycated human CD59 loses its MAC-inhibitory function, and (iii) inactivation of CD59 increases MAC-induced growth factor release from endothelial cells. We demonstrate by site-directed mutagenesis that residues K41 and H44 form a preferential glycation motif in human CD59. The presence of this glycation motif in human CD59, but not in CD59 of other species, may help explain the distinct propensity of humans to develop vascular proliferative complications of diabetes.
Heparan Sulfate-based Treatments for Regenerative Medicine (2011)

This review summarizes the emerging strategies that exploit the glycosaminoglycan sugar, heparan sulfate (HS), either as a substitute for, or as a supplement to growth factor (GF) therapy for regenerative medicine. Excluding autograft, the administration of GFs is currently the most effective treatment for critical bone repair and restoration. However, major hurdles in the clinical development of GF therapies include the high cost, the unwanted side effects, and the toxicity associated with the physiological overdosing required to achieve a successful outcome. These drawbacks may be overcome with the application of particular HS fractions that have been optimized to bind, recruit and enhance the biological activity of endogenous GF at the site of injury. Three HS-based treatments are discussed here: first, the single, localized, and sustained delivery of HS as a stand-alone therapeutic agent; then, the inclusion of an HS component within a delivery device so as to stabilize and potentiate the bioactivity of the incorporated GF; and finally, the growing use of HS mimetics, particularly for bone repair.
Characterization of Human Endothelin B Receptor and Mutant Receptors Expressed in Insect Cells (1997)

Endothelin type-B receptor (ET(B)R) forms a stable complex with its ligand, endothelin-1. To facilitate biochemical and biophysical studies of human ET(B)R, several ET(B)R mutants carrying a hexahistidine tag sequence at the N or C terminus were expressed in Sf9 cells and were purified by a combination of biotinylated endothelin-1-ligand-affinity and nickel-affinity chromatographies. The ligand-free receptor was purified by dissociating the ligand x receptor complex with 2 M NaSCN, whereas the ligand-bound ET(B)R was purified by the use of thiol-sensitive biotinylated endothelin-1. While the wild-type ET(B)R was expressed at about 100 pmol 125I-endothelin-1-binding activity/mg membrane protein, the deletion of 36 residues from the N-terminus reduced the expressed activity to about 30%. On the other hand, the lack of glycosylation and the replacement of 2-9 residues in the N-terminal tail resulted in a 20-40% reduction in the expressed activity. Among the mutant proteins, [H57-H62, G63-G65]ET(B)R, carrying six His residues in the N-terminal tail, was studied extensively because it was purified most effectively. Ligand-free [H57-H62, G63-G65]ET(B)R, purified in digitonin, retained full ligand-binding activity, while other detergents led to partial denaturation of the receptor after solubilization or after elution with NaSCN. On the other hand, ligand-bound [H57-H62, G63-G65]ET(B)R could be purified in various detergents, such as n-octyl-beta-D-glucopyranoside or n-decyl-beta-D-maltopyranoside. Ligand-free [H57-H62, G63-G65]ET(B)R reconstituted in phospholipid vesicles stimulated the binding of guanosine 5'-3-O-(thio)triphosphate by Gq in the presence of endothelin-1. Ligand-bound [H57-H62, G63-G65]ET(B)R showed similar catalytic activity in nucleotide exchange by Gq. These results indicate that the ligand x receptor complex in a detergent-micellar solution retained the biologically active structure, and that the presence of ligand, endothelin-1, in the receptor molecule reinforces the stable assembly of a helical bundle and therefore the active structure.
Managing massive time series streams with multi-scale compressed trickles (2009)

We present Cypress, a novel framework to archive and query massive time series streams such as those generated by sensor networks, data centers, and scientific computing. Cypress applies multi-scale analysis to decompose time series and to obtain sparse representations in various domains (e.g. frequency domain and time domain). Relying on the sparsity, the time series streams can be archived with reduced storage space. We then show that many statistical queries such as trend, histogram and correlations can be answered directly from compressed data rather than from reconstructed raw data. Our evaluation with server utilization data collected from real data centers shows significant benefit of our framework.
Lipid Association-induced N- and C-terminal Domain Reorganization in Human Apolipoprotein E3 (2001)

Apolipoprotein E (apoE) is a 299 amino acid, anti-atherogenic protein that plays a key role in regulating plasma lipoprotein metabolism. It is composed of an N-terminal (NT) domain (residues 1-191) that is responsible for binding to members of the low density lipoprotein receptor family and a C-terminal (CT) domain (residues 216-299) that anchors the protein to lipoprotein particles by virtue of its high-affinity lipid binding characteristics. Isoform-specific differences in the NT domain that modulate the lipoprotein binding preference elicited by the CT domain suggest the existence and importance of domain interactions in this protein. Employing steady state fluorescence quenching and resonance energy transfer techniques, spatial proximity relationships between the N- and C-terminal domains were investigated in recombinant human apoE3. ApoE3 containing a single Trp at position 264 and an N-iodoacetyl-N'-(5-sulfo-1-napthyl) ethylenediamine (AEDANS) moiety covalently attached to the lone Cys residue at position 112 was used (AEDANS-apoE3/W@264). Fluorescence quenching studies revealed a solvent-exposed location for Trp-264. In the lipid-free state, fluorescence resonance energy transfer (FRET) was noted between Trp-264 and AEDANS, with a calculated distance of 27 A between the two fluorophores. Control experiments established that FRET observed in this system is intramolecular. FRET was abolished upon proteolysis in the linker region connecting the NT and CT domains. Lowering the solution pH to 4 induced an increase in the efficiency of intramolecular energy transfer, with the two domains reorienting about 5 A closer to one another. Interdomain FRET was retained in the presence of 0.6-1.0 m guanidine hydrochloride but was lost at higher concentrations, a manifestation of unfolding of the domains and increased distance between the donor-acceptor pair. Interaction of AEDANS-apoE3/W@264 with lipid induced a loss of FRET, attributed to spatial repositioning of the domains by >80 A. The data provide biophysical evidence that, in addition to reported conformational changes in the four-helix bundle configuration induced by lipid association, lipid binding of apoE is accompanied by reorientation of the tertiary disposition of the NT and CT domains.