gebhart/patrepeval huggingface dataset:
Recent Advances in Classical and Non-Classical Antifolates as Antitumor and Antiopportunistic Infection Agents: Part II (2008)

Antifolates that inhibit the key enzymes thymidylate synthase (TS) and dihydrofolate reductase (DHFR) have found clinical utility as antitumor and antiopportunistic agents. Methotrexate {MTX, (1)} and 5-fluorouracil (5-FU) were among the first clinically useful DHFR and TS inhibitors, respectively. The development of resistance to 5-FU, its occasional unpredictable activity and toxicity resulted in the search of novel antifolates. Pemetrexed (4) and raltitrexed (5) are newer antifolates that specifically inhibit TS, and are clinically useful as antitumor agents. A major mechanism of tumor resistance to clinically useful antifolates is based on their need for polyglutamylation via the enzyme folylpoly-gamma-glutamate synthetase (FPGS). Recently, classical antifolates that do not need to be polyglutamylated have also been developed and include plevitrexed (6) and GW1843 (7). Nolatrexed (8), trimethoprim {TMP, (11)} and piritrexim {PTX, (12)} are nonclassical antifolates for antitumor and parasitic chemotherapy that passively diffuse into cells and hence do not have to depend on FPGS or the reduced folate carrier (RFC). Structural requirements for inhibition with antifolates have been studied extensively and novel agents that exploit key interactions in the active site of TS, DHFR, FPGS, and RFC have been proposed. This two-part review discusses the design, synthesis and structural requirements for TS and DHFR inhibition and their relevance to antitumor and parasitic chemotherapy, since 1996. Monocyclic and 6-5 fused bicyclic antifolates were discussed in Part I. The 6-6 bicyclic and tricyclic antifolates will be discussed here in Part II.
Functional and Nonfunctional LamB Signal Sequences Can Be Distinguished by Their Biophysical Properties (1989)

The role of the signal sequence in the secretion of proteins remain unclear despite extensive research. We have examined properties of synthetic peptides corresponding to a family of signal sequences derived from the lamB gene of Escherichia coli, including five examples of known phenotype that contain mutations in the signal sequence. By circular dichroism spectroscopy, the wild type and export-component mutant signal peptides show a high alpha-helix content in membrane mimetic environments (sodium dodecyl sulfate micelles and phospholipid vesicles). Tendency to adopt helical conformations is clearly not sufficient to define a functional signal sequence, however, as some nonfunctional mutant signal peptides also contain a relatively high proportion of alpha-helix. The affinity of these peptides for phospholipid monolayers as assessed by surface tensiometry reveals further distinguishing properties. Export-competent peptides show an increased affinity for and greater perturbation of phospholipid monolayers and bilayers than to export-defective peptides. These results suggest a lipid binding role for the signal sequence during protein export in addition to its recognition by proteins of the export pathway.
Intranasal Administration of Drugs (2008)

Previous failure of therapy with locally applied drugs in the case of sinonasal smell disorders may be partly due to the fact that the drugs did not reach the olfactory cleft when using traditional forms of application (ie, sprays). However, using an applicator producing squirts seems likely to present the drugs more effectively to the olfactory epithelium. Thus, it may be hypothesized that therapy could be more effective using a squirt system.
Quasiparticle band structure based on a generalized Kohn-Sham scheme (2007)

We present a comparative full-potential study of generalized Kohn-Sham (gKS) schemes with explicit focus on their suitability as starting point for the solution of the quasiparticle equation. We compare ${G}_{0}{W}_{0}$ quasiparticle band structures calculated upon local-density approximation (LDA), screened-exchange, HSE03, PBE0, and Hartree-Fock functionals for exchange and correlation (XC) for Si, InN, and ZnO. Furthermore, the HSE03 functional is studied and compared to the generalized gradient approximation (GGA) for 15 nonmetallic materials for its use as a starting point in the calculation of quasiparticle excitation energies. For this case, the effects of self-consistency in the $GW$ self-energy are also analyzed. It is shown that the use of a gKS scheme as a starting point for a perturbative quasiparticle correction can improve upon the deficiencies found for LDA or GGA starting points for compounds with shallow $d$ bands. For these solids, the order of the valence and conduction bands is often inverted using local or semilocal approximations for XC, which makes perturbative ${G}_{0}{W}_{0}$ calculations unreliable. The use of a gKS starting point allows for the calculation of fairly accurate band gaps even in these difficult cases, and generally single-shot ${G}_{0}{W}_{0}$ calculations following calculations using the HSE03 functional are very close to experiment.
Activation and Caspase-mediated Inhibition of PARP: A Molecular Switch between Fibroblast Necrosis and Apoptosis in Death Receptor Signaling (2002)

Death ligands not only induce apoptosis but can also trigger necrosis with distinct biochemical and morphological features. We recently showed that in L929 cells CD95 ligation induces apoptosis, whereas TNF elicits necrosis. Treatment with anti-CD95 resulted in typical apoptosis characterized by caspase activation and DNA fragmentation. These events were barely induced by TNF, although TNF triggered cell death to a similar extent as CD95. Surprisingly, whereas the caspase inhibitor zVAD prevented CD95-mediated apoptosis, it potentiated TNF-induced necrosis. Cotreatment with TNF and zVAD was characterized by ATP depletion and accelerated necrosis. To investigate the mechanisms underlying TNF-induced cell death and its potentiation by zVAD, we examined the role of poly(ADP-ribose)polymerase-1 (PARP-1). TNF but not CD95 mediated PARP activation, whereas a PARP inhibitor suppressed TNF-induced necrosis and the sensitizing effect of zVAD. In addition, fibroblasts expressing a noncleavable PARP-1 mutant were more sensitive to TNF than wild-type cells. Our results indicate that TNF induces PARP activation leading to ATP depletion and subsequent necrosis. In contrast, in CD95-mediated apoptosis caspases cause PARP-1 cleavage and thereby maintain ATP levels. Because ATP is required for apoptosis, we suggest that PARP-1 cleavage functions as a molecular switch between apoptotic and necrotic modes of death receptor-induced cell death.
A New Data Selection Approach for Semi-Supervised Acoustic Modeling (2006)

Current approaches to semi-supervised incremental learning prefer to select unlabeled examples predicted with high confidence for model re-training. However, this strategy can degrade the classification performance rather than improve it. We present an analysis for the reasons of this phenomenon, showing that only relying on high confidence for data selection can lead to an erroneous estimate to the true distribution when the confidence annotator is highly correlated with the classifier in the information they use. We propose a new data selection approach to address this problem and apply it to a variety of applications, including machine learning and speech recognition. Encouraging improvements in recognition accuracy are observed in our experiments
In vivo assessment of neovascularization of liver metastases using perfusion CT. (1998)

Neovascularization of tumours produces a high microvessel density. Although diagnostic imaging is unable to visualize microvessels directly, it is possible to demonstrate associated changes in tissue perfusion. The aim of this study was to use the quantitative functional information and high spatial resolution of perfusion computed tomography to study neovascularization of hepatic metastases. Perfusion CT was performed in 13 patients with hepatic metastases from various primary tumours. Arterial perfusion was measured in the metastasis; both arterial and portal perfusion were measured in a small rim of liver tissue immediately adjacent to the metastasis. Perfusion measurements were correlated against survival of the patient in nine cases. Arterial perfusion was increased above normal values, both in the metastasis (median: 0.62 ml min-1 ml-1; range: 0.26-3.05 ml min-1 ml-1) and in the adjacent liver (median: 0.51 ml min-1 ml-1; range: 0.14-1.60 ml min-1 ml-1). Portal perfusion of adjacent liver was highly variable (median: 0.30 ml min-1 ml-1; range: 0.05-1.85 ml min-1 ml-1). Arterial perfusion was positively correlated with portal perfusion within liver tissue adjacent to metastases (p < 0.05, r = 0.58), a reversal of the normal situation. Survival of the patient correlated with arterial perfusion within the metastasis (p < 0.05, r = 0.69) but more closely with arterial perfusion in the adjacent liver (p < 0.02, r = 0.78). In conclusion, alterations in perfusion within metastases and adjacent liver are in accordance with the histological features of neovascularization. Perfusion CT offers a method for studying neovascularization in the living patient and offers prognostic information.
On a More Accurate Assessment of Scaled Copper/Low-k Interconnects Performance (2007)

Interconnect RC delay, predominantly affected by the effective dielectric constant (k-value) and by the copper resistivity (rho <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Cu</sub> ), is an important performance metric for back-end-of-line (BEOL) process assessment. As process technology scales, interpretation of fundamental process-induced RC delay variations becomes a challenge as the relative importance of statistical process-induced fluctuations (variation of critical dimensions during plasma etching of low-k materials, line profiles, thickness nonuniformity, etc.) grows rapidly and begins to show. A more accurate interpretation of experimental data and prediction of future performance trends requires a more realistic assessment that accounts for such statistical fluctuations. In this paper, an inventory of the most common possible sources of statistical process-induced RC delay variations is made, parameterized, and subsequently used to generate a realistic 2-D interconnect model from which, R and C, and thereby RC delay, are computed. For both wire resistivity and RC, response surface models (RSM) are subsequently generated based on the results of a full factorial design-of-experiment analysis with these input parameters. Finally, based on the RSMs, an improved methodology of interconnect performance evaluation is proposed.
A TEM nanoanalytical investigation of Pd/Ge ohmic contacts for the miniaturization and optimization of n-InGaAs MOSFET devices (2010)

In this paper, a nanoanalytical investigation of electron beam evaporated PdGe ohmic contacts onto an n+ In0.53Ga0.47As layer using electron energy loss spectroscopy (EELS) is presented. The chemical information reported in this paper has been obtained using EELS spectrum images (SI) that allow not only depth resolution but also spatial resolution which is essential in such inhomogeneous systems.
Inhibition of Diacylglycerol Acyltransferase by Betulinic Acid from<i>Alnus hirsuta</i> (2006)

During the screening for diacylglycerol acyltransferase (DGAT) inhibitors from natural products, the lupane-type triterpenoid betulinic acid was isolated from the methanol extract of Alnus hirsuta. It potently inhibited DGAT in the rat liver microsomes with an IC (50) value of 9.6 microM. Enzyme kinetic studies showed apparent Km and Ki values of 13.3 microM and 8.1 microM using [(14)C]oleoyl-CoA as a substrate. A decrease in the apparent Vmax was observed with betulinic acid, whereas the apparent Km remained constant. Therefore, a Lineweaver-Burk plot of DGAT inhibition by betulinic acid showed a non-competitive type of inhibition. In the cell-based assay, betulinic acid inhibited triglyceride (TG) formation by human HepG2 cells. These findings suggest that betulinic acid may be a potential lead compound in the treatment of obesity.
Infrared reflectance evaluation of chemically vapor deposited β-SiC films grown on Si substrates (1986)

We use infrared reflectance from 400 to 4000 cm−1 to evaluate cubic SiC films grown by chemical vapor deposition on Si substrates. From different regions of the spectra we determine precise film thicknesses, estimate carrier concentrations in highly doped specimens, observe roughness at both film surfaces, and detect conducting regions at the interface. We show how the roughness and the interfacial conducting region introduce nonideality into the spectra. The method is nondestructive and the information can be obtained in less than 1 h after film growth.
Aerobic, Diselenide-Catalyzed Redox Dehydration: Amides and Peptides (2018)

At 2.5 mol % loadings using reaction temperatures between 30–55 °C, ortho-functionalized diaryl diselenides are highly effective organocatalytic oxidants for aerobic redox dehydrative amidic and peptidic bond formation using triethyl phosphite as a simple terminal reductant. This simple-to-perform organocatalytic reaction relies on the ability of selenols to react directly with dioxygen in air without recourse to metal catalysts. It represents an important step toward the development of a general, economical, and benign catalytic redox dehydration protocol.
Purification and characterization of a novel human acidic nuclease/intra-cyclobutyl-pyrimidine-dimer-DNA phosphodiesterase (2000)

A novel N-glycosylated, mannose-rich protein has been purified approx. 4000-fold from human liver in a seven-step procedure including ion-exchange chromatography and fractionation on concanavalin A-Sepharose, Sephadex G-75 and oligo(dT)-cellulose matrices. The molecular mass of the protein is 46 kDa when measured by gel filtration (i.e. under non-denaturing conditions) and 60 kDa by SDS/PAGE (i.e. under denaturing conditions). The protein possesses two DNA backbone-incising activities, namely, the random introduction of single-strand breaks in native DNA and the rupture of the phosphodiester linkage internal to cyclobutyl pyrimidine dimers, the major class of DNA lesions induced by solar UV rays. Both activities are optimal at pH 5.0 in vitro, although the non-specific nuclease displays appreciable activity at neutral pH, depending on the buffer composition. The protein has been named acidic nuclease/intra-cyclobutyl-pyrimidine-dimer-DNA phosphodiesterase (AN/IDP). As a nuclease, the protein ‘prefers#x2019; a linear DNA structure over a covalently closed circular molecule and is more proficient at digesting single-stranded than double-stranded DNA. The polynucleotide cleavage products of the nuclease contain 5ʹ-OH and 3ʹ-PO4 termini, which are refractory to direct rejoining by DNA ligases. Depending on the substrate, the nuclease activity exhibits a temperature optimum of 50 °C or greater, and is neither stimulated by Mg2+ or Ca2+ nor inhibited by Zn2+. AN/IDP is present in human liver and in cultured human cells of both fibroblastic and lymphocytic origins. Intracellularly, the protein can be readily detected in both the cytosolic and nuclear fractions, although much more (approx. 3-fold) is found in the latter fraction. We propose that this bifunctional enzyme may be involved in both apoptotic DNA digestion and metabolism of cyclobutyl pyrimidine dimers in UV-irradiated human cells.
The Tunneling Time of an Electron (1967)

There is a widely spread misconception regarding the physical significance of the various tunneling times currently used to describe metal-insulator-metal tunneling phenomena. Using quantum mechanics, the transition time of an electron tunneling from a state on one side of the barrier to a state on the other side can be determined. This time is the period of interaction between the\nelectron and the barrier, since before and after the transition, the electron is in a quantum state of one of the metals. Furthermore, the RC time constant of the sandwich-like device and the electron transition or interaction time are equivalent representations\nof the same physical parameter. But none of these times is the quasiclassical "transmission time" analyzed by Hartman, which has become widely accepted as the electron-barrier interaction time, although this was clearly not his intention. In this communication we wish to point out that it is the (quantum mechanical) transition time which is the characteristic time of tunneling phenomena.
Data exchange (2003)

Data exchange is the problem of taking data structured under a source schema and creating an instance of a target schema that reflects the source data as accurately as possible. Given a source instance, there may be many solutions to the data exchange problem, that is, many target instances that satisfy the constraints of the data exchange problem. In an earlier paper, we identified a special class of solutions that we call universal. A universal solution has homomorphisms into every possible solution, and hence is a "most general possible" solution. Nonetheless, given a source instance, there may be many universal solutions. This naturally raises the question of whether there is a "best" universal solution, and hence a best solution for data exchange. We answer this question by considering the well-known notion of the core of a structure, a notion that was first studied in graph theory, but has also played a role in conjunctive-query processing. The core of a structure is the smallest substructure that is also a homomorphic image of the structure. All universal solutions have the same core (up to isomorphism); we show that this core is also a universal solution, and hence the smallest universal solution. The uniqueness of the core of a universal solution together with its minimality make the core an ideal solution for data exchange. Furthermore, we show that the core is the best among all universal solutions for answering unions of conjunctive queries with inequalities. After this, we investigate the computational complexity of producing the core. Well-known results by Chandra and Merlin imply that, unless P = NP, there is no polynomial-time algorithm that, given a structure as input, returns the core of that structure as output. In contrast, in the context of data exchange, we identify natural and fairly broad conditions under which there are polynomial-time algorithms for computing the core of a universal solution. Finally, we analyze the computational complexity of the following decision problem that underlies the computation of cores: given two graphs G and H, is H the core ofG? Earlier results imply that this problem is both NP-hard and coNP-hard. Here, we pinpoint its exact complexity by establishing that it is a DP-complete problem.
Synthesis and characterization of poly{hexakis[(methyl)(4‐hydroxyphenoxy)]cyclotriphosphazene} (2001)

The reaction of methylhydroquinone with hexachlorocyclotriphosphazene in the presence of a base, 4-picoline, in cyclohexane was investigated. Nuclear magnetic resonance spectroscopy, multiangle laser light scattering, and elemental analyses were performed on the product and two other related phosphazene materials produced by analogous synthetic routes: poly[hexakis(4-hydroxyphenoxy)cyclotriphosphazene] (1) and hexakis[(3-tert-butyl)(4-hydroxyphenoxy)]cyclotriphosphazene (2). Unlike the data for 2 where the tert-butyl moiety enforced regiospecific nucleophilic addition, the data for the methylhydroquinone-substituted cyclotriphosphazene product indicate that the less sterically bulky methyl group provides only limited protection for the adjacent hydroxyl group. The result is the formation of a low molecular weight oligomer, poly{hexakis[(methyl)(4-hydroxyphenoxy)]cyclotriphosphazene} (3), instead of a discrete cyclic trimer species. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 82: 3439–3446, 2001
Human Naive CD8 T Cells Down-Regulate Expression of the WNT Pathway Transcription Factors Lymphoid Enhancer Binding Factor 1 and Transcription Factor 7 (T Cell Factor-1) following Antigen Encounter In Vitro and In Vivo (2006)

The transcription factors lymphoid enhancer binding factor 1 (LEF1) and transcription factor 7 (TCF7) (T cell factor-1 (TCF-1)) are downstream effectors of the WNT signaling pathway, which is a critical regulator of T cell development in the thymus. In this study, we show that LEF1 and TCF7 (TCF-1) are not only expressed in thymocytes, but also in mature T cells. Our data demonstrate that Ag encounter in vivo and engagement of the TCR or IL-15 receptor in vitro leads to the down-regulation of LEF1 and TCF7 (TCF-1) expression in human naive CD8 T cells. We further show that resting T cells preferentially express inhibitory LEF1 and TCF7 (TCF-1) isoforms and that T cell activation changes the isoform balance in favor of stimulatory TCF7 (TCF-1) isoforms. Altogether, our study suggests that proteins involved in the WNT signaling pathway not only regulate T cell development, but also peripheral T cell differentiation.
Blind spot size depends on the optic disc topography: a study using SLO controlled scotometry and the Heidelberg retina tomograph (1997)

The size of scotomas depends on the surface topography of the tested area. The prominent nasal part of the optic disc appears less 'blind' than the shallow temporal part, probably because of more intensive light scattering by the prominent nasal part of the disc. These considerations should also apply to other scotomas.
ETUDE, a recursive dialog manager with embedded user interface patterns (2005)

We describe ETUDE, a dialog manager that supports recursive descriptions of the dialog flow in spoken dialog applications. We also introduce the notion of user interface patterns, i.e. those dialog patterns that are frequently used in applications. We then describe how these patterns can be built into the dialog manager engine in order to facilitate the design and development of complex applications.
Chemistry in superacids. 7. Superacid-catalyzed isomerization of endo- to exo-trimethylenenorbornane (tetrahydrodicyclopentadiene) and to adamantane (1986)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemistry in superacids. 7. Superacid-catalyzed isomerization of endo- to exo-trimethylenenorbornane (tetrahydrodicyclopentadiene) and to adamantaneGeorge A. Olah and Omar FarooqCite this: J. Org. Chem. 1986, 51, 26, 5410–5413Publication Date (Print):December 1, 1986Publication History Published online1 May 2002Published inissue 1 December 1986https://pubs.acs.org/doi/10.1021/jo00376a067https://doi.org/10.1021/jo00376a067research-articleACS PublicationsRequest reuse permissionsArticle Views481Altmetric-Citations31LEARN 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