gebhart/patrepeval huggingface dataset:
Synthesis of Protein Farnesyltransferase and Protein Geranylgeranyltransferase Inhibitors:  Rapid Access to Chaetomellic Acid A and Its Analogues (1996)

A facile two-step stereospecific synthesis of the protein farnesyltransferase inhibitor chaetomellic acid A (1) and its analogues was developed. Addition of organocuprates derived from Grignard reagents (e.g. tetradecylmagnesium chloride and CuBr.Me(2)S) to dimethyl acetylenedicarboxylate (DMAD) in tetrahydrofuran containing hexamethylphosphoramide was followed by capture of the resulting copper enolates with a variety of electrophiles (e.g. methyl iodide) to give dimethyl cis-butenedioate derivatives 4-11. Hydrolysis with lithium hydroxide generated the corresponding lithium carboxylates, which readily closed to 2,3-disubstituted maleic anhydrides 17-20 upon acid treatment. Compound 16, an analogue wherein the tetradecyl group of 1 is replaced by a farnesyl moiety, is 7-fold more potent than 1 as an inhibitor of protein farnesyltransferase from yeast and displays a 100:1 selectivity for this enzyme relative to yeast protein geranylgeranyltransferase. In contrast, analogue 15, which contains a geranylgeranyl side chain, shows ca. 10:1 selectivity for the latter enzyme.
Dispersion-managed mode locking (1999)

The pulse shape and spectrum of ultrashort-pulse Ti:sapphire mode-locked lasers are explained by a model akin to dispersion-managed pulse propagation of optical communications. The pulse is characterized as a nonlinear Bloch wave in a periodic structure. The ultimate spectral width is limited by dispersion and mirror bandwidth and less strongly by gain filtering. The main role of Kerr-lens mode locking is to provide stability against noise buildup. One-dimensional computer simulations are sufficient to explain the major pulse-shaping dynamics. Results are compared with experiment.
ANTERIOR ENDOSCOPIC L5-S1 INTERBODY SPINAL FUSION – LONG-TERM OUTCOME STUDY (2005)

L5-S1 interbody fusion is a successful technique for treating patients with isolated degenerative disc disease. Traditionally through an open technique, the anterior laparoscopic approach for this was first described in 1991. The purpose of this study was to review the long-term outcome results of L5-S1 interbody spinal fusion, using an anterior endoscopic technique, performed on patients with isolated degenerative L5-S1 disc disease. The first 41 spinal fusions performed by the senior authors were analysed. Patients received clinical, functional and radiological review by an independent assessor. Clinical outcomes were excellent with >90% of patients having significant improvement in back assessment scores (Fraser and Greenough, Japanese Orthopaedic Association). There were no intraoperative complications, no vascular complications, and no reports of retrograde ejaculation. The anterior endoscopic approach for L5-S1 inter-body fusion results in good clinical outcomes, with a very low rate of morbidity. Surgical recovery time is quicker compared to open techniques, however, two skilled surgeons and an increase in theatre resources is required.
The implementation and evaluation of a theory for high level cognitive skill acquisition through expert systems modelling techniques (1989)

From previous studies by Koubek and Salvendy (1988), it has been established that differences exist in the high level controlled processes between expert (E) and super-expert (SE) subjects on computer program modification tasks. This study examines the implications of this finding by applying modelling techniques via expert systems technology. To examine the hypothesis that the knowledge representation is critical to SE performance, and to indicate how these results might have practical application, two small prototype expert systems were developed using the E and SE knowledge representations respectively. A qualitative analysis reveals significant performance differences between systems attributable to the knowledge representation and suggests a combination of E and SE knowledge be used for construction of a hybrid expert system. The SE knowledge base is a hierarchical structure and is organized under abstract categories, suggesting a breadth first approach. This structure allows for interactions within the program itself and between the program and user environment. The E knowledge base is narrow and task specific, indicating a depth first approach. In conclusion, theoretical and practical implications of this research into SE performance and modelling techniques are discussed.
Model-based design of stimulus waveforms for selective microstimulation in the central nervous system (2003)

Cable models of neurons were used to design stimulus waveforms to activate selectively targeted neuronal populations in the CNS. Anodic first biphasic waveforms enabled selective stimulation of fibers, while cathodic first biphasic waveforms enabled selective stimulation of cells. The results demonstrate how the non-linear properties of the neural elements can be manipulated to achieve selective stimulation in the CNS.
Strain relaxation and surface morphology of compositionally graded Si/Si1−xGex buffers (1998)

Systematic studies of strain relaxation were performed in a series of compositionally graded SiGe buffer layers grown without and with a subsequent constant composition SiGe layer by x-ray reciprocal space mapping techniques. The analysis of these experiments yields depth dependent strain values as well as misfit dislocation densities. The higher the grading rate (%Ge/μm) the higher the residual in-plane strain at the epitaxial surface. Atomic force microscopy studies show that the rms surface roughness increases systematically with increasing final Ge content of the graded layers and rises with increasing grading rate.
Comparison of electrolyzed oxidizing water with various antimicrobial interventions to reduce Salmonella species on poultry (2002)

Foodborne pathogens in cell suspensions or attached to surfaces can be reduced by electrolyzed oxidizing (EO) water; however, the use of EO water against pathogens associated with poultry has not been explored. In this study, acidic EO water [EO-A; pH 2.6, chlorine (CL) 20 to 50 ppm, and oxidation-reduction potential (ORP) of 1,150 mV], basic EO water (EO-B; pH 11.6, ORP of -795 mV), CL, ozonated water (OZ), acetic acid (AA), or trisodium phosphate (TSP) was applied to broiler carcasses inoculated with Salmonella Typhimurium (ST) and submerged (4 C, 45 min), spray-washed (85 psi, 25 C, 15 s), or subjected to multiple interventions (EO-B spray, immersed in EO-A; AA or TSP spray, immersed in CL). Remaining bacterial populations were determined and compared at Day 0 and 7 of aerobic, refrigerated storage. At Day 0, submersion in TSP and AA reduced ST 1.41 log10, whereas EO-A water reduced ST approximately 0.86 log10. After 7 d of storage, EO-A water, OZ, TSP, and AA reduced ST, with detection only after selective enrichment. Spray-washing treatments with any of the compounds did not reduce ST at Day 0. After 7 d of storage, TSP, AA, and EO-A water reduced ST 2.17, 2.31, and 1.06 log10, respectively. ST was reduced 2.11 log10 immediately following the multiple interventions, 3.81 log10 after 7 d of storage. Although effective against ST, TSP and AA are costly and adversely affect the environment. This study demonstrates that EO water can reduce ST on poultry surfaces following extended refrigerated storage.
Heterocyclic Substituted Amino Acids via a,b-Dehydroamino Acid Derivatives. Studies on Amino Acids III (1983)

Condensat~ons of lactam acetals 2g.b with isocyanacetlc esters --.give 2 3 .5 The 2-configuration of 33 . .(RI=CH3, R2=C2H51 was determined by X-ray diffraction.Reaction with ethyl N-(ethoxycarbony1)glycinate gives the protected a.8-dehydroammo acid derivatives 4. The isocyano group can be converted to the carbamategroup via the isocyanates 2. Catalytic hydrogenation of the double bond and deprotection of the functional groups give the amino acids !is, b and 19.Efforts towards the synthesis of a,D-unsaturated amino acids and peptides continue unabated 2a-g .Heterocyclic derivatives of a m m o acids show interesting pharmacologic 9)properties.Towards our synthesis of streptolutin we planned to check the C-C bond connectron of lactam acetals wlth ammo acid derivatives.-cyanates 2 .
Revisión judicial y democracia deliberativa en términos de teoría departamental y constitucionalismo popular / Judicial Review and Deliberative Democracy in terms of Departmentalism and Popular Constitutionalism (2017)

El trabajo discute algunos aspectos de la legitimidad de la supremacía judicial desde un punto de vista histórico y normativo. Adicionalmente, reflexiona sobre las teorías político-constitucionales conocidas como departamentalismo y constitucionalismo popular. A continuación, enuncia y descarta como válidos diversos argumentos prácticos y normativos que defienden la supremacía judicial, es decir, el carácter final con que los tribunales controlan normas emanadas de otros poderes del Estado. Finalmente, nos valdremos de la distinción entre republicanismo y liberalismo para argumentar que la única justificación de la supremacía judicial puede proveerla una comprensión liberal e instrumental de la democracia, la cual consideramos insuficiente desde una perspectiva republicana y deliberativa.Palabras clave: constitucionalismo, revisión judicial, supremacía judicial, departamentalismo, democracia deliberativa.AbstractThe essay discusses some aspects of the legitimacy of the idea of judicial supremacy from a historical and a normative viewpoint. Additionally, it reflects upon the political and constitutional theories known as departmentalism and popular constitutionalism. It further describes and discard the validity of several practical and abstract arguments that champion judicial supremacy, i.e. the finality with which courts of law control norms enacted by other branches of government. Finally, we use the distinction between republicanism and liberalism to argue that the justification of judicial supremacy can only be provided by a liberal and instrumental comprehension of democracy, which is an insufficient justification from a republican and deliberative perspective.Keywords: constitutionalism, judicial review, judicial supremacy, departmentalism, deliberative democracy.
Titania Coatings on Monodisperse Silica Spheres (Characterization Using 2-Propanol Dehydration and TEM) (1996)

Titania coatings ranging from sub-monolayer to ≈7 nm thick have been deposited on silica by hydrolysis of titanium alkoxide precursors. Nonporous model silica particles of spherical shape were used as the support for titania. The ratio of titanium alkoxide to water and the dilution of the reactant mixture in ethanol control the nature of the coating. If the alkoxide concentration is too high, precipitation of second-phase titania particles occurs rather than a uniform coating. On the other hand, higher water concentrations led to aggregated spheres being connected with titania necks. Isolated silica spheres with uniform coatings of titania are obtained when the alkoxide concentration is kept low. The samples were studied using transmission and scanning electron microscopy. 2-Propanol dehydration was used as a probe reaction, since it was found that reactivity for propene formation is directly correlated with anatase surface area. Using this correlation, the effective titania surface area of each sample could be derived. However, it was found that the correlation does not work for titania/silica samples heated to temperatures less than 673 K, since the titania remains amorphous. Hence a 773 K calcination was used to convert the titania to anatase before deriving effective titania surface areas. Agreement between the BET surface area and the effective titania surface area implies that complete coverage of the silica has been achieved in our study.
Biodegradable poly(ether‐ester) multiblock copolymers for controlled release applications: An in vivo evaluation (2004)

Multiblock poly(ether-ester)s based on poly(ethylene glycol), butylene terephthalate, and butylene succinate segments were evaluated for their in vivo degradation and biocompatibility in order to establish a correlation with previously reported in vitro results. Porous polymer sheets were implanted subcutaneously for 32 weeks in rats. The degradation was monitored visually (histology), by molecular weight (GPC), and by copolymer composition (NMR). Substitution of the aromatic terephthalate units by aliphatic succinate units was shown to accelerate the degradation rate of the copolymers. Direct correlation of the in vivo and in vitro degradation of the porous implants showed a slightly faster initial molecular weight decrease in vivo. Besides hydrolysis, oxidation occurs in vivo due to the presence of radicals produced by inflammatory cells. In addition, the higher molecular weight plateau of the residue found in vivo indicated a higher solubility of the oligomers in the extracellular fluid compared to a phosphate buffer. Minor changes in the poly(ether-ester) compositions were noted due to degradation. Microscopically, fragmentation of the porous implants was observed in time. At later stages of degradation, macrophages were observed phagocytozing small polymer particles. Both in vitro cytotoxicity studies and histology on in vivo samples proved the biocompatibility of the poly(ether-ester)s.
Consequences of Comorbid Insomnia Symptoms and Sleep-Related Breathing Disorder in Elderly Subjects (2006)

Because insomnia comorbid with SRBD is associated with the greatest functional impairment, and SRBD is commonly found in the elderly population, health care providers should also consider SRBD in elderly patients with insomnia symptoms.
Efficient green thermally activated delayed fluorescence (TADF) from a phenoxazine–triphenyltriazine (PXZ–TRZ) derivative (2012)

Efficient thermally activated delayed fluorescence (TADF) was developed in a material based on a phenoxazine (PXZ) electron donor unit and a 2,4,6-triphenyl-1,3,5-triazine (TRZ) electron acceptor unit. An organic light-emitting diode containing this novel TADF emitter layer was fabricated and exhibited a maximum external quantum efficiency of 12.5% with green emission.
Why Britain's drug czar mustn't wage war on drugs (1997)

The British government has advertised the first ever post of drug supremo, or 'drug czar' to borrow the term used in the United States. It is good news that the new Labour government is evidently serious about the growing national and international drug problem and intends to strengthen further the pan-departmental approach taken by the central drugs co-ordinating unit and its strategic document for England, Tackling Drugs Together .1

But there is a grave danger that the increased political attention could backfire, producing a more politicised approach to the problem and causing the new czar's dominant orientation to be one of control. Crime dominated posturing would lead to a damaging dissociation between the public appeal of the policy and actual evidence of effectiveness. It could lead to a mistaken bias to funding more panda cars, prisons, and pop propaganda instead of evidence-based treatment, rehabilitation, and preventive strategies. In contrast, diverting limited resources from enforcement to treatment and rehabilitation would result in more cost-effective crime …
Epitaxial liftoff of GaAs detectors onto silicon integrated circuits (2002)

The seperation of thin film epitaxial devices from the growth substrated is called epitaxial lift off, and the subsequent transfer and bonding of these thin film devices to smooth substrates such as Si integrated circuits is studied.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Tyrosine phosphorylation of phospholipase C-gamma 1 induced by cross-linking of the high-affinity or low-affinity Fc receptor for IgG in U937 cells. (1992)

The human monocytic cell line U937 possesses two classes of the IgG Fc receptor (Fc gamma R), a high-affinity 72-kDa Fc gamma R (Fc gamma RI) and a low-affinity 40-kDa Fc gamma R (Fc gamma RII). Cross-linking of either class of Fc gamma R in U937 cells elicits an increase in the concentration of free intracellular Ca2+. A rapid rise in the concentration of inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) and of several other inositol phosphates derived from Ins-1,4,5-P3 was observed after cross-linking of Fc gamma Rs in U937 cells. This result suggests that Ins-1,4,5-P3, generated by the action of phospholipase C (PLC), acts as a second messenger by which Fc gamma Rs mobilize intracellular Ca2+ in U937 cells. The mechanism by which the cross-linking of Fc gamma Rs triggers activation of PLC was studied. Cross-linking of Fc gamma RI or Fc gamma RII resulted in a rapid and transient phosphorylation of PLC-gamma 1 on tyrosine residues. It has previously been shown that phosphorylation of PLC-gamma 1 on tyrosine residues activates its enzymatic activity in cells. Prior incubation of U937 cells with a protein tyrosine kinase inhibitor, herbimycin A, prevented the tyrosine phosphorylation of PLC-gamma 1 and the hydrolysis of phosphatidylinositol 4,5-bisphosphate induced by the cross-linking of Fc gamma Rs. Thus, Fc gamma RI and Fc gamma RII appear to be functionally coupled to a nonreceptor tyrosine kinase that phosphorylates PLC-gamma 1 after receptor cross-linking, thereby causing activation of PLC-gamma 1.
CALCITONIN GENE-RELATED PEPTIDE: UNDERSTANDING ITS ROLE (2004)

Calcitonin gene-related peptide (CGRP), a 37 amino acid neuropeptide, identified in multiple species, has widespread distribution and expression. CGRP acts through G protein-coupled receptors whose presence and changes in function modulate the peptide's effects in various tissues. Three receptor subtypes have been identified and CGRP's signal transduction through the receptors is dependent on two accessory proteins: Receptor activity modifying protein1 (RAMP1) and Receptor component protein (RCP). Several endogenous substances such as glucocorticoids, nitric oxide (NO), nerve growth factors (NGF), and steroid hormones modulate CGRP release and synthesis. Both peptide and non-peptide agonists and antagonists of CGRP receptors are being developed. Also the therapeutic benefits of some antagonists such as BIBN 4096 BS in migraine have been promising. This brief review provides a preliminary understanding of the diverse biological effects of the peptide in various systems. The current status of CGRP and its receptors in many pathophysiological states is not fully explored and future findings are greatly awaited.
Neuregulin 1 Allosterically Enhances the Antitumor Effects of the Noncompeting Anti-HER3 Antibody 9F7-F11 by Increasing Its Binding to HER3 (2017)

Exploratory clinical trials using therapeutic anti-HER3 antibodies strongly suggest that neuregulin (NRG1; HER3 ligand) expression at tumor sites is a predictive biomarker of anti-HER3 antibody efficacy in cancer. We hypothesized that in NRG1-expressing tumors, where the ligand is present before antibody treatment, anti-HER3 antibodies that do not compete with NRG1 for receptor binding have a higher receptor-neutralizing action than antibodies competing with the ligand for binding to HER3. Using time-resolved-fluorescence energy transfer (TR-FRET), we demonstrated that in the presence of recombinant NRG1, binding of 9F7-F11 (a nonligand-competing anti-HER3 antibody) to HER3 is increased, whereas that of ligand-competing anti-HER3 antibodies (H4B-121, U3-1287, Ab#6, Mab205.10.2, and MOR09825) is decreased. Moreover, 9F7-F11 showed higher efficacy than antibodies that compete with the ligand for binding to HER3. Specifically, 9F7-F11 inhibition of cell proliferation and of HER3/AKT/ERK1/2 phosphorylation as well as 9F7-F11-dependent cell-mediated cytotoxicity were higher in cancer cells preincubated with recombinant NRG1 compared with cells directly exposed to the anti-HER3 antibody. This translated <i>in vivo</i> into enhanced growth inhibition of NRG1-expressing BxPC3 pancreatic, A549 lung, and HCC-1806 breast cell tumor xenografts in mice treated with 9F7-F11 compared with H4B-121. Conversely, both antibodies had similar antitumor effect in NRG1-negative HPAC pancreatic carcinoma cells. In conclusion, the allosteric modulator 9F7-F11 shows increased anticancer effectiveness in the presence of NRG1 and thus represents a novel treatment strategy for NRG1-addicted tumors. <i>Mol Cancer Ther; 16(7); 1312-23. ©2017 AACR</i>.
ZD1839, AN EPIDERMAL GROWTH FACTOR TYROSINE KINASE INHIBITOR SELECTED FOR CLINICAL DEVELOPMENT (1997)

Woodburn, J. R.; Barker, A. J.; Gibson, K. H.; Ashton, S. E.; Wakeling, A. E.; Curry, B. J.; Scarlett, L.; Henthorn, L. R. Author Information
Reflectant Induced Modification of Soybean Canopy Radiation Balance V. Longwave Radiation Balance1 (1976)

Abstract Potential water‐savings and increased water use efficiency may result from reflectant‐induced modification of the canopy radiation balance. This report is one of a series of papers describing reflectant treatment effects on the radiation balance. The objective of this study was to evaluate the effect of the reflectant treatment on the longwave balance over soybeans [ Glycine max (L.) Merr.]. Average ratios of the flux densities of net longwave to global radiation on 3 and 9 August, were 0.251, 0.239, 0.257, and 0.241 over ‘Amsoy’ treated, Amsoy untreated, ‘Beeson’ treated, and Beeson untreated areas, respectively. Corresponding global radiation reflection coefficients were 0.207, 0.194, 0.235, and 0.211. The flux density of outgoing longwave radiation was greater from the reflectorized crop than from the untreated crop. This was due both to an increase in the reflection of incoming longwave radiation and to an increase in the flux density of emitted radiation. The increased reflection of longwave radiation was due to a reduction in the longwave absorptivity; the increased emission was caused by the higher temperature of the treated canopy. The reduction of net radiation over the treated areas resulted from the increased outgoing longwave radiation and from the increased reflection of global radiation. Both processes contributed about equally to the observed differences in the net radiative fluxes between treated and untreated canopies. A mechanism of radiation balance modification by reflectants is proposed to explain the observed changes in net radiation.
Loss of CD8 and TCR binding to Class I MHC ligands following T cell activation (2005)

The capacity of T cells to bind peptide/MHC ligands changes with T cell development and differentiation. Here we study changes in peptide/MHC multimer binding following T cell activation. Surprisingly, T cell activation caused a marked reduction in specific peptide/MHC Class I multimer binding, which was distinct from transient TCR down-regulation, and was especially dramatic for engagement with low-affinity peptide/MHC ligands. Direct CD8-Class I interactions were also profoundly and rapidly impaired following T cell stimulation, even though surface CD8alpha and CD8beta levels were unchanged after activation, suggesting that decreased CD8 co-receptor binding contributes to this effect. Finally, we show that enzymatic desialylation restores much of the multimer binding on activated T cells, suggesting that altered glycosylation may inhibit TCR/CD8 binding to peptide/MHC ligands. These radical changes in activated T cells' ability to perceive peptide/MHC ligands may contribute to selective outgrowth of clones with high affinity for the stimulatory ligand.