gebhart/patrepeval huggingface dataset:
Overcoming the Resistance Hurdle: Pharmacokinetic-Pharmacodynamic Target Attainment Analyses for Rezafungin (CD101) against Candida albicans and Candida glabrata (2018)

Rezafungin (CD101) is a novel echinocandin antifungal agent with activity against <i>Aspergillus</i> and <i>Candida</i> species, including azole- and echinocandin-resistant isolates. The objective of these analyses was to conduct pharmacokinetic (PK)-pharmacodynamic (PD) target attainment analyses to evaluate single and once-weekly rezafungin dosing to provide dose selection support for future clinical studies. Using a previously developed rezafungin population PK model, Monte Carlo simulations were conducted utilizing the following three intravenous rezafungin regimens: (i) a single 400 mg dose, (ii) 400 mg for week 1 followed by 200 mg weekly for 5 weeks, and (iii) 400 mg weekly for 6 weeks. Percent probabilities of achieving the nonclinical PK-PD targets associated with net fungal stasis and 1-log<sub>10</sub> CFU reductions from baseline for <i>Candida albicans</i> and <i>Candida glabrata</i> were calculated for each rezafungin regimen. At the MIC<sub>90</sub> for <i>C. albicans</i> and <i>C. glabrata</i>, a single 400 mg dose of rezafungin achieved probabilities of PK-PD target attainment of ≥90% through week 3 of therapy for all PK-PD targets evaluated. When evaluating the multiple-dose (i.e., weekly) regimens under these conditions, percent probabilities of PK-PD target attainment of 100% were achieved through week 6. Moreover, high (>90%) probabilities of PK-PD target attainment were achieved through week 6 following administration of the weekly regimens at or above the MIC<sub>100</sub> values for <i>C. albicans</i> and <i>C. glabrata</i> based on contemporary <i>in vitro</i> surveillance data. These analyses support the use of single and once-weekly rezafungin regimens for the treatment of patients with candidemia and/or candidiasis due to <i>C. albicans</i> or <i>C. glabrata</i>.
Polymers tethered to curves interfaces: a self-consistent-field analysis (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolymers tethered to curves interfaces: a self-consistent-field analysisN. Dan and M. TirrellCite this: Macromolecules 1992, 25, 11, 2890–2895Publication Date (Print):May 1, 1992Publication History Published online1 May 2002Published inissue 1 May 1992https://pubs.acs.org/doi/10.1021/ma00037a016https://doi.org/10.1021/ma00037a016research-articleACS PublicationsRequest reuse permissionsArticle Views630Altmetric-Citations144LEARN 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
Open-Angle Glaucoma (1993)

Our understanding of glaucoma has undergone dramatic changes in the past decade. The ferment has derived from new epidemiologic information, improved diagnostic methods, and developments in surgical and drug therapy. This review concentrates on primary open-angle glaucoma, the most prevalent form of the disorder in Western countries.DefinitionPrimary open-angle glaucoma usually affects both eyes and combines a particular abnormal appearance of the optic disk (optic-nerve head) with a slowly progressive loss of visual sensitivity (Figure 1). The characteristic appearance of the glaucomatous optic disk is visible by ophthalmoscopy (Figure 2). The present standard for determining visual loss in glaucoma . . .
Thermal conductivity measurements on Silurian limestones from the Island of Gotland, Sweden (1982)

The thermal conductivity of compact limestones was measured by means of the transient needle-probe method in the field and in the laboratory as well, A comparison of the two procedures indicates that the laboratory measurements are the most representative ones because of a better control of the influence from the surroundings. The water-saturated limestone samples measured under laboratory conditions have thermal conductivities of 2.52 - 3.34 W m-1 К-1 and densities.pf 2520-2690 kg/m3, which are in agreement with standard values. The thermal conductivities were found to increase with increasing density, and a linear correlation of K„ = 4.18- 10˜Jp — 7.97 (W m"' K˜') was obtained as a first approximation by the least squares method. □ Thermal conductivity, density, limestone, Silurian, Gotland, southeastern Sweden, N5650 N5800 EI930 EI800.
Airline Seat Allocation with Multiple Nested Fare Classes (1993)

This paper addresses the problem of determining optimal booking policies for multiple fare classes that share the same seating pool on one leg of an airline flight when seats are booked in a nested fashion and when lower fare classes book before higher ones. We show that a fixed-limit booking policy that maximizes expected revenue can be characterized by a simple set of conditions on the subdifferential of the expected revenue function. These conditions are appropriate for either the discrete or continuous demand cases. These conditions are further simplified to a set of conditions that relate the probability distributions of demand for the various fare classes to their respective fares. The latter conditions are guaranteed to have a solution when the joint probability distribution of demand is continuous. Characterization of the problem as a series of monotone optimal stopping problems proves optimality of the fixed-limit policy over all admissible policies. A comparison is made of the optimal solutions with the approximate solutions obtained by P. Belobaba using the expected marginal seat revenue (EMSR) method.
Probing circulating tumor cells in microfluidics (2013)

Circulating tumor cells (CTCs) are important targets for study as we strive to better understand, diagnose, and treat cancers. However, CTCs are found in blood at extremely low concentrations; this makes isolation, enrichment, and characterization of CTCs technically challenging. Recently, the development of CTC separation devices has grown rapidly in both academia and industry. Part of this development effort centered on microfluidic platforms, exploiting the advantages of microfluidics to improve CTC separation performance and device integration. In this Focus article, we highlight some of the recent work in microfluidic CTC separation and detection systems and discuss our appraisal of what the field should do next.
Mixtures of charged colloids and nonadsorbing flexible polyelectrolytes: An integral equation study (2000)

We study the equilibrium and structural properties of mixtures of like-charged colloids and nonadsorbing flexible polyelectrolytes using liquid state integral equations. The polymer chains in the semidilute regime are treated within the polymer reference interaction site model. The monomers and the colloids interact via screened Coulomb potentials (Debye–Hückel level). The electrostatic interactions between the different macromolecules inside the solution are responsible for complex local structures and rich phase diagrams, which depend on the charges and on the Debye screening length. The pair correlations between colloids are interpreted in terms of the effective, polymer-averaged, colloid–colloid pair potential. A first-order picture indicates that the Coulombic depletion attraction due to the osmotic pressure of the semidilute network against the colloidal particles dominates the direct repulsion at high enough monomer concentration and induces the liquid–liquid phase separation. Higher-order effects involving correlations inside the polyelectrolyte system alter this simple picture.
The Role of the Lysyl Binding Site of Tissue-type Plasminogen Activator in the Interaction with a Forming Fibrin Clot (1995)

To describe the role of the lysyl binding site in the interaction of tissue-type plasminogen activator (t-PA, FGK1K2P) with a forming fibrin clot, we performed binding experiments with domain deletion mutants GK1K2P, K2P, and the corresponding point mutants lacking the lysyl binding site in the absence and the presence of epsilon-amino caproic acid (EACA). Occupation of the lysyl binding site in the K2 domain with EACA has a pronounced effect on the binding of FGK1K2P to a fibrin clot (C50 = 77 +/- 11 nM versus 376 +/- 45 nM with EACA). Deleting the lysyl binding site in the K2 domain (substitution D236N) also impairs fibrin binding but to a lesser extent (C50 = 169 +/- 20 nM). Although the binding of K2P to a fibrin clot is weak (C50 = 1163 +/- 490 nM), it still is 2 orders of magnitude stronger than the binding of EACA to K2P. Therefore it was surprising to find that deletion of the lysyl binding site in K2P completely abolishes fibrin binding. Even when both the F domain and the lysyl binding site were deleted, considerable fibrin binding is still observed (C50 = 557 +/- 126 nM), suggesting other than F and K2-mediated interactions. The binding of FGK1K2P, FGK1K2P (D236N), GK1K2P, and GK1K2P (D236N) to fibrin could be competitively inhibited by FGK1K2P and K2P, indicating that all molecules recognize the same interaction sites on a fibrin clot. Based on these results, a new model for the interaction of t-PA with a forming fibrin clot is proposed. The fibrin binding sites in t-PA are not confined to the F and K2 domain. The main role of the lysyl binding site in the K2 domain of t-PA appears indirect rather than direct, most likely stabilizing a conformation favorable for fibrin binding.
Characterization of urinary calculi: in vitro study of "twinkling artifact" revealed by color-flow sonography. (1998)

An in vitro relationship exists between the twinkling artifact and the morphology of urinary stones. Color-flow sonography could play a role in detecting dense calcium oxalate monohydrate calculi, which in turn may help predict fragmentability.
Current diagnostic concepts to detect coronary artery disease in women (2008)

The goal of non-invasive diagnostic testing is to detect coronary artery disease (CAD) timely and with optimal fidelity. In women, the accuracy of most functional diagnostic investigations is diminished compared with men. To minimize the sex-related bias in detection of CAD, there is a need for a non-invasive test strategy capable of risk-stratifying women, and of identifying subsets of patients in need of further invasive testing. The present review discusses the validity of classical diagnostic procedures for CAD in women, and addresses the relevance of newer techniques in the context of a female-specific diagnostic approach.
Topical CPP-ACP crèmes: beyond caries prevention (2014)

Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP) is a unique naturally derived protein-based remineralizing technology which is used globally in chewing gums (such Recaldent ™) and topical cremes (such as GC Tooth Mousse ™. and Tooth Mousse Plus ™). Phosphopeptides are derived from milk caseins are complexed with amorphous calcium phosphate, to form stable complexes which are nanoparticles of some 2 nm in diameter with a large surface area (Cross et al. 2006). CPP-ACP complexes act as biological calcium phosphate delivery vehicles, and are able to boost levels of bioavailable calcium and phosphate in saliva and plaque fluid without causing indiscriminate precipitation of calcium salts. This makes this material particularly effective in the remineralization of early enamel lesions, and in the treatment of other types of enamel opacities. As such, the range of clinical applications now extends beyond altering the demin/remin balance for human enamel to treating hypoplastic enamel and other types of enamel opacities
Tunable Surface-Enhanced Raman Scattering from Large Gold Nanoparticle Arrays (2001)

Raman signal enhancements in excess of 10(7) can be achieved at near-infrared wavelengths when mid-nanometer sized gold particles self-organize into close-packed planar arrays. These substrates generate stable surface-enhanced Raman scattering which changes dramatically as a function of periodic structure and excitation wavelength.
A nanoscale single-molecule amplifier and its consequences (1998)

Our ability to manipulate atoms and molecules on an individual basis has opened a new experimental frontier that makes feasible the quest for single molecular-scale devices as successors to the transistor. Here, we discuss our realization of the first amplifier using a single fullerene molecule less than 1 nm in diameter as the active element. This C/sub 60/ molecular device works by electromechanical modulation of virtual resonance quantum mechanical tunneling. The equivalent of the grid is achieved by the purely mechanical action of compressing the C/sub 60/ cage voltage. This action reversibly changes the internal electronic structure of the molecule, increasing its conductance in a continuous manner. The first embodiment provides experimental verification with a measured voltage gain of five. The implications of these results indicate a new approach to electronics on the nanoscale, working in a new transport regime for the three-terminal devices. Going beyond these experiments, we discuss possible approaches of creating single-molecule devices and the advantages they promise.
Receptors of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) in fetal and adult human kidney (1998)

Vascular endothelial growth factor (VEGF) has an important function in renal vascular ontogenesis and is constitutively expressed in podocytes of the adult kidney. The ability of VEGF to be chemotactic for monocytes and to increase the activity of collagenase and plasminogen activator may have implications for renal development and renal disease. In humans, the cellular actions of VEGF depend on binding to two specific receptors: Flt-1 and KDR. The aims of this study were: (1) to localize VEGF receptor proteins in human renal ontogenesis; (2) to quantify VEGF binding in human fetal and adult kidney; and (3) to dissect the binding into its two known components: the KDR and Flt-1 receptors. The latter aim was achieved by competitive binding of VEGF and placenta growth factor-2, which only binds to Flt-1. Quantification of 125I-VEGF binding sites was performed by autoradiography and computerized densitometry. By double-label immunohistochemistry, VEGF receptor proteins were localized solely to endothelial cells of preglomerular vessels, glomeruli, and postglomerular vessels. In developing glomeruli, VEGF receptor protein appeared as soon as endothelial cells were positive for von Willebrand factor. Specific 125I-VEGF binding could be localized to renal arteries and veins, glomeruli, and the tubulointerstitial capillary network in different developmental stages. Affinity (Kd) of adult (aK) and fetal (fK) kidneys was: Kd: glomeruli 38.6 +/- 11.2 (aK, n = 5), 36.3 +/- 7.1 (fK, n = 5); cortical tubulointerstitium 19.4 +/- 2.6 (aK, n = 5), 11.6 +/- 7.0 (fK, n = 5) pmol. Placenta growth factor-2 displaced VEGF binding in all renal structures by approximately 60%. VEGF receptor proteins thus were found only in renal endothelial cells. A coexpression of both VEGF binding sites could be shown, with Flt-1 demonstrating the most abundant VEGF receptor binding sites in the kidney. These studies support the hypothesis of a function for VEGF in adult kidney that is independent of angiogenesis.
A computational procedure for determining energetically favorable binding sites on biologically important macromolecules (1985)

The interaction of a probe group with a protein of known structure is computed at sample positions throughout and around the macromolecule, giving an array of energy values. The probes include water, the methyl group, amine nitrogen, carboxy oxygen, and hydroxyl. Contour surfaces at appropriate energy levels are calculated for each probe and displayed by computer graphics together with the protein structure. Contours at negative energy levels delineate contours also enable other regions of attraction between probe and protein and are found at known ligand binding clefts in particular. The contours also enable other regions of attraction to be identified and facilitate the interpretation of protein-ligand energetics. They may, therefore, be of value for drug design.
MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription (2008)

Mutations in the gene encoding the transcriptional repressor methyl-CpG binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome. Loss of function as well as increased dosage of the MECP2 gene cause a host of neuropsychiatric disorders. To explore the molecular mechanism(s) underlying these disorders, we examined gene expression patterns in the hypothalamus of mice that either lack or overexpress MeCP2. In both models, MeCP2 dysfunction induced changes in the expression levels of thousands of genes, but unexpectedly the majority of genes (approximately 85%) appeared to be activated by MeCP2. We selected six genes and confirmed that MeCP2 binds to their promoters. Furthermore, we showed that MeCP2 associates with the transcriptional activator CREB1 at the promoter of an activated target but not a repressed target. These studies suggest that MeCP2 regulates the expression of a wide range of genes in the hypothalamus and that it can function as both an activator and a repressor of transcription.
Membrane properties of isolated mudpuppy taste cells. (1988)

The voltage-dependent currents of isolated Necturus lingual cells were studied using the whole-cell configuration of the patch-clamp technique. Nongustatory surface epithelial cells had only passive membrane properties. Small, spherical cells resembling basal cells responded to depolarizing voltage steps with predominantly outward K+ currents. Taste receptor cells generated both outward and inward currents in response to depolarizing voltage steps. Outward K+ currents activated at approximately 0 mV and increased almost linearly with increasing depolarization. The K+ current did not inactivate and was partially Ca++ dependent. One inward current activated at -40 mV, reached a peak at -20 mV, and rapidly inactivated. This transient inward current was blocked by tetrodotoxin (TTX), which indicates that it is an Na+ current. The other inward current activated at 0 mV, peaked at 30 mV, and slowly inactivated. This more sustained inward current had the kinetic and pharmacological properties of a slow Ca++ current. In addition, most taste cells had inwardly rectifying K+ currents. Sour taste stimuli (weak acids) decreased outward K+ currents and slightly reduced inward currents; bitter taste stimuli (quinine) reduced inward currents to a greater extent than outward currents. It is concluded that sour and bitter taste stimuli produce depolarizing receptor potentials, at least in part, by reducing the voltage-dependent K+ conductance.
Cardiovascular Effects of n-3 Fatty Acids (1988)

ALTHOUGH earlier studies1 2 3 suggested that dietary fish had some properties that could potentially prevent coronary artery disease, it was not until the epidemiologic studies of Bang et al.4 and Dyerberg et al.5 in the mid-1970s that the association became noteworthy. These researchers reviewed reports of a low prevalence of atherosclerosis among Eskimos in Greenland and subsequent documentation of an age-adjusted mortality from myocardial infarction among the Greenland Eskimos that was approximately 1/10th that among Danes6 or North Americans, despite a diet as high in fat and cholesterol as that of the Danes or Americans. The striking difference between the diets . . .
RNA polymerase III promoter and terminator elements affect Alu RNA expression (1995)

Promoter elements derived from the 7SL RNA gene stimulate RNA polymerase III (Pol III) directed Alu transcription in vitro. These elements also stimulate expression of Alus transfected into 293 cells, but transcripts from these same constructs are undetectable in HeLa cells. A terminator resembling the terminator for the 7SL RNA gene has no effect on in vitro Alu template activity, but increases expression in vivo in a position independent manner. Alu transcripts generated from templates with and without this terminator have identical half-lives, indicating that this terminator stimulates expression by increasing template activity. Together, these results show that Alu expression may be regulated at multiple levels and can respond to cis-acting elements. This new found ability to express Alu transcripts by transient transfection provides an opportunity to monitor their post-transcriptional fate. Primary Alu transcripts are not extensively adenylated or deadenylated following transcription, but are short-lived compared to 118 nt scAlu RNA. In addition to Alu RNA, transfected templates encode scAlu RNA, but very high levels of Alu RNA expression does not increase the abundance of scAluRNA. ScAluRNA is not merely a transient RNA degradation product, but is instead tightly regulated by factors other than the abundance of primary transcripts.
Thermal and optical properties of bulk GaN crystals fabricated through hydride vapor phase epitaxy with void-assisted separation (2005)

The fundamental material parameters associated with GaN, which are important for the design of devices such as light-emitting diodes and laser diodes, were investigated using large high-quality GaN single crystals fabricated through hydride vapor phase epitaxy using the void-assisted separation method. The thermal-expansion coefficients (298–573K) along the C[0001], A[112¯0], and M[101¯0] axes (αC, αA, and αM) were measured. Thermal expansion in each direction, approximately proportional to the temperature, was observed throughout the measured temperature range. Although the thermal-expansion coefficients in the high-temperature range, i.e., αC(573K)=7.2±0.02×10−6∕K, αA(573K)=5.7±0.2×10−6∕K, and αM(573K)=5.8±0.2×10−6∕K,were relatively close to the reported values, the thermal-expansion coefficients along the C axis in the low-temperature range, i.e., αC(298K)=5.3±0.02×10−6∕K, was significantly larger than the reported values. Thermal conductivities parallel and perpendicular to the C axis were almost the same, i.e., 2.0±0.1Wcm−1K−1. This value is close to the values reported on the low-dislocation density part of epitaxially laterally overgrown GaN. This could indicate that the defect density of our crystals is very low and that the defects are distributed uniformly throughout the volume. The wavelength dependence of the refractive index and the optical-absorption coefficient was also investigated.