gebhart/patrepeval huggingface dataset:
AMPA Receptor Antagonists (2001)

AMPA Receptor antagonists have received considerable attention in recent years. Within the class of excitatory amino acid receptor antagonists AMPA receptor antagonists have shown excellent neuroprotection in several models of cerebral ischemia and neuronal injury. However, poor physical properties have been a major limiting factor in developing these as viable drug candidates. The quinoxaline-2,3-dione template has been the backbone of various competitive AMPA receptor antagonists such as NBQX, PNQX, YM-90K and more recently ZK200775. The SAR learned from these have been valuable for developing the AMPA pharmacophore model (Fig. 2) and has been discussed in detail in this review. There have been efforts in this area to design very selective AMPA receptor antagonists by minimizing the interaction at the NMDA associated GlyN receptors. Compounds designed by BASF and Yamanouchi have been successful in these efforts and their compounds show excellent affinity for the AMPA receptors. Efforts by Warner-Lambert and Novartis also highlight significant success in developing balanced AMPA and GlyN receptor antagonists. Non-competitive AMPA receptor antagonists are also being pursued for various neurological disorders including neuroprotection and are divided in two major classes, viz. positive and negative allosteric modulators. The physical properties of negative allosteric modulators such as GYKI 52466, which belong to the 2,3-benzodiazepinyl structural class have been significantly better. However, the in vitro activity of these compounds has been in the micromolar range and the overall class has the disadvantage of not having a high throughput assay. Other classes of compounds such as phthalazines and quinazolines are being developed and have raised hopes for the second generation of compounds in this area.
Phosphoramidate ProTides of 2′-C-Methylguanosine as Highly Potent Inhibitors of Hepatitis C Virus. Study of Their in Vitro and in Vivo Properties (2010)

Hepatitis C virus infection constitutes a serious health problem in need of more effective therapies. Nucleoside analogues with improved exposure, efficacy, and selectivity are recognized as likely key components of future HCV therapy. 2'-C-Methylguanosine triphosphate has been known as a potent inhibitor of HCV RNA polymerase for some time, but the parent nucleoside is only moderately active due to poor intracellular phosphorylation. We herein report the application of phosphoramidate ProTide technology to bypass the rate-limiting initial phosphorylation of this nucleoside. Over 30 novel ProTides are reported, with variations in the aryl, ester, and amino acid regions. l-Alanine compounds are recognized as potent and selective inhibitors of HCV in replicon assay but lack rodent plasma stability despite considerable ester variation. Amino acid variation retaining the lead benzyl ester moiety gives an increase in rodent stability but at the cost of potency. Finally l-valine esters with ester variation lead to potent, stable compounds. Pharmacokinetic studies on these agents in the mouse reveal liver exposure to the bioactive triphosphate species following single oral dosing. Systemic exposure of the ProTide and parent nucleoside are low, indicating possible low toxicity in vivo, while liver concentrations of the active species may be predictive of efficacy in the clinic. This represents one of the most thorough cross-species studies of ProTides to date.
Estriol ameliorates autoimmune demyelinating disease (1999)

Estriol as a hormone involved in immune changes during pregnancy may provide a basis for the novel therapeutic use of estriol for MS and other putative Th1-mediated autoimmune diseases that improve during late pregnancy.
Semiconductor Nanomembrane Tubes: Three-Dimensional Confinement for Controlled Neurite Outgrowth (2011)

In many neural culture studies, neurite migration on a flat, open surface does not reflect the three-dimensional (3D) microenvironment in vivo. With that in mind, we fabricated arrays of semiconductor tubes using strained silicon (Si) and germanium (Ge) nanomembranes and employed them as a cell culture substrate for primary cortical neurons. Our experiments show that the SiGe substrate and the tube fabrication process are biologically viable for neuron cells. We also observe that neurons are attracted by the tube topography, even in the absence of adhesion factors, and can be guided to pass through the tubes during outgrowth. Coupled with selective seeding of individual neurons close to the tube opening, growth within a tube can be limited to a single axon. Furthermore, the tube feature resembles the natural myelin, both physically and electrically, and it is possible to control the tube diameter to be close to that of an axon, providing a confined 3D contact with the axon membrane and potentially insulating it from the extracellular solution.
Oxidation of Methionine Residues in Antithrombin (1999)

Commercially available human plasma-derived preparations of the serine protease inhibitor antithrombin (AT) were shown to contain low levels of oxidation, and we sought to determine whether oxidation might be a means of regulating the protein's inhibitory activity. A recombinant form of AT, with similarly low levels of oxidation as purified, was treated with hydrogen peroxide in order to study the effect of oxidation, specifically methionine oxidation, on the biochemical properties of this protein. AT contains two adjacent methionine residues near the reactive site loop cleaved by thrombin (Met314 and Met315) and two exposed methionines that border on the heparin binding region of AT (Met17 and Met20). In forced oxidations with hydrogen peroxide, the methionines at 314 and 315 were found to be the most susceptible to oxidation, but their oxidation did not affect either thrombin-inhibitory activity or heparin binding. Methionines at positions 17 and 20 were significantly oxidized only at higher concentrations of peroxide, at which point heparin affinity was decreased. However at saturating heparin concentrations, activity was only marginally decreased for these highly oxidized samples of AT. Structural studies indicate that highly oxidized AT is less able to undergo the complete conformational change induced by heparin, most probably due to oxidation of Met17. Since this does not occur in less oxidized, and presumably more physiologically relevant, forms of AT such as those found in plasma preparations, oxidation does not appear to be a means of controlling AT activity.
Positronium annihilation data and actual free-volume distribution in polymers (2007)

Determination of the size distribution of free-volume holes in solids, in particular, polymers, is an important physicochemical problem. The positron annihilation technique has been proposed for this purpose. The central point in this technique is the quantitative interpretation of data, especially, for substances with a high specific surface area. A developed free-volume system in open-pore membrane materials, such as poly(trimethylsilylpropyne) PTMSP and the spirocyclically bound benzodioxane polymer PIM-1, and polymeric sorbents (hypercrosslinked polystyrenes) makes it possible for the first time to compare the sorption characteristics and positron annihilation data on the character of size distribution of nanopores in these polymers. In combination with the results of mathematical simulation of the structure and radiothermoluminescence measurements, the array of data indicate the structural inhomogeneity of the test amorphous materials. It was shown that this inhomogeneity in relation to the positron annihilation technique is expressed in the insufficiency of the representation of the orthopositronium decay curve by one component that takes into account the Gaussian lifetime distribution (symmetrical pore size distribution) and in the necessity of use of several decay components. The feasibility of revealing a nonrandom character of pore size distribution gives the positron annihilation technique an advantage over other approaches (inverse gas chromatography, 129Xe NMR) to investigation of nanopores in polymers.
An algebraic formula for amplitudes of intermodulation products involving an arbitrary number of frequencies (1968)

Given a nonlinear device described by a power series and having an input consisting of a sum of any number of cosine waves, a formula is derived which enables one to express the amplitude of any chosen intermodulation product in the output as a function of the power series coefficients and the amplitudes of the input frequency components.
Detection of β-human chorionic gonadotropin mRNA as a marker for cutaneous malignant melanoma (1996)

The beta chain of human chorionic gonadotropin (hCG) hormone is produced by fetal cells, gonadal cell tumors and several types of non-gonadal carcinoma. hCG is composed of an alpha and a beta chain, the latter of which can be used to distinguish the molecule from other related gonadotropin hormones. Detection of beta-hCG mRNA transcripts can be potentially useful as a marker to identify tumor cells. We devised a highly specific and sensitive assay to detect the atavistic expression of beta-hCG in cutaneous melanoma by RT-PCR. Twenty-four melanoma cell lines and 43 melanoma biopsies were evaluated for beta-hCG mRNA expression. An RT-PCR assay was developed to specifically distinguish beta-hCG poly-A mRNA from other related gonadotropin beta chains. This was performed by endonuclease digestion of a unique Sty 1 site in the beta chain, followed by Southern blot analysis with a beta-hCG cDNA probe. Of the 24 melanoma cell lines analyzed, 18 expressed beta-hCG mRNA. Analysis of melanoma biopsy specimens revealed beta-hCG mRNA expression in 17/25 melanoma-positive TDLN, and in only 5/15 non-lymphoid melanoma metastases. Beta-hCG mRNA expression had a 53% correlation to tyrosinase mRNA, a predominant melanoma marker. Beta-hCG mRNA was not detected in normal donor PBL and normal lymph nodes. Detection of beta-hCG mRNA expression may be a useful molecular marker to define a subset of malignant melanoma.
The Anti-allergic Cromones: Past, Present, and Future (2017)

The anti-allergic cromones were originally synthesized in the 1960s by Fisons Plc, and the first drug to emerge from this program, disodium cromoglycate was subsequently marketed for the treatment of asthma and other allergic conditions. Whilst early studies demonstrated that the ability of the cromones to prevent allergic reactions was due to their 'mast cell stabilizing' properties, the exact pharmacological mechanism by which this occurred, remained a mystery. Here, we briefly review the history of these drugs, recount some aspects of their pharmacology, and discuss two new explanations for their unique actions. We further suggest how these findings could be used to predict further uses for the cromones.
Vasoactive intestinal peptide modulates proinflammatory mediator synthesis in osteoarthritic and rheumatoid synovial cells (2004)

Our observations confirm that the proposed anti-inflammatory actions of VIP in murine models also apply to human synovial cells ex vivo. Further studies are encouraged to evaluate the use of VIP as a potential therapy for chronic inflammatory joint diseases.
Low claudin-6 expression correlates with poor prognosis in patients with non-small cell lung cancer (2015)

Low claudin-6 expression is an independent prognostic biomarker that indicates a worse prognosis in patients with NSCLC.
Lodamin (PEG-PLA-TNP-470), a novel formulation for oral administration of TNP-470 as a potent antiangiogenic and anti-cancer drug. (2008)

1118 Targeting angiogenesis, the formation of new blood vessels, is becoming an important strategy for cancer therapy. TNP-470, an analog of fumagillin, is among the most potent inhibitors of angiogenesis. This drug has broader antiangiogenic activity than most known drugs, as demonstrated in numerous animal tumor models.  In clinical trials, TNP-470 showed significant inhibition of tumors, including durable complete regression (Kudelka AP et al. N Engl J Med 338, 991-2, 1998). The clinical efficacy of TNP-470 was limited by neurotoxicity that was solved by the development of Caplostatin, an HPMA polymer conjugate of TNP-470 (formulation for injection) (Satchi-Fainaro et al., Nature Medicine 10, 255-261, 2004, Satchi-Fainaro et al., Cancer Cell 7, 251-61, 2005).  However, a major clinical limitation still remains: The TNP-470 has a poor oral availability and short plasma half-life (minutes), necessitating frequent continuous parenteral administration as an infusion of 1-4 hr a few times a week.  We have now addressed these issues, and report here for the first time a formulation for oral administration of TNP-470, named Lodamin. TNP-470 is conjugated to a copolymer: poly(ethylene-glycol)-poly(lactic)acid (PEG-PLA). The conjugation is then self-assembled into polymeric-micelles, where TNP-470 is located in the core, and protected from the acidic environment of the stomach, thus enabling oral availability.  Lodamin has a spherical morphology as shown by transmission electron microscopy (10-100 nm). The release kinetics of TNP-470 from Lodamin was determined in-vitro at pH 1.2 and 7.4 and revealed a slow release for up to 28 days.  In-vitro, Lodamin was rapidly taken up by endothelial cells as demonstrated by confocal microscopy and flow cytometry, and significantly inhibited cell proliferation.  Lodamin was effectively absorbed in the intestineand remained active. A corneal micropocket assay, in which the angiogenic response was measured 6 days after implantation of VEGF pellets, showed that oral Lodamin inhibited VEGF-induced vessel growth by 40%. In tumor-bearing mice, Lodamin effectively inhibited tumor growth of both subcutaneous Lewis Lung Carcinoma (~87%) and B16/F10 melanoma (~77%), while oral free TNP-470 did not affect tumor growth. Histological sections of the tumors showed that oral Lodamin decreased angiogenesis and proliferation of tumor cells.  Biodistribution experiments showed Lodamin to be concentrated in tumors without penetration into the brain. Furthermore, unlike free TNP-470, oral Lodamin did not cause TNP-470-related neurological impairment, as tested by the ability of mice to walk on a narrow-beam without losing their balance.  Therefore, we report Lodamin as a first in its class compound of oral antiangiogenic, non-toxic, anti-cancer drugs that can be chronically administered for cancer therapy or for prevention of tumor recurrence.
Compressive Channel Estimation and Tracking for Large Arrays in mm-Wave Picocells (2016)

We propose and investigate a compressive architecture for estimation and tracking of sparse spatial channels in millimeter (mm) wave picocellular networks. The base stations are equipped with antenna arrays with a large number of elements (which can fit within compact form factors because of the small carrier wavelength) and employ radio frequency (RF) beamforming, so that standard least squares adaptation techniques (which require access to individual antenna elements) are not applicable. We focus on the downlink, and show that “compressive beacons,” transmitted using pseudorandom phase settings at the base station array, and compressively processed using pseudorandom phase settings at the mobile array, provide information sufficient for accurate estimation of the two-dimensional (2D) spatial frequencies associated with the directions of departure of the dominant rays from the base station, and the associated complex gains. This compressive approach is compatible with coarse phase-only control, and is based on a near-optimal sequential algorithm for frequency estimation which approaches the Cramér Rao Lower Bound. The algorithm exploits the geometric continuity of the channel across successive beaconing intervals to reduce the overhead to less than 1% even for very large (32 × 32) arrays. Compressive beaconing is essentially omnidirectional, and hence does not enjoy the SNR and spatial reuse benefits of beamforming obtained during data transmission. We therefore discuss system level design considerations for ensuring that the beacon SNR is sufficient for accurate channel estimation, and that inter-cell beacon interference is controlled by an appropriate reuse scheme.
Plasmid transformation and replica filter plating of Acholeplasma laidlawii (1990)

The restriction deficient mutant 8195 of Acholeplasma laidlawii strain JA1 was transformed by the promiscuous streptococcal plasmid vector pNZ18 at a frequency of 4 x 10(-4)/cfu. The plasmid was maintained without structural rearrangements but was lost in the absence of a selection pressure, i.e. kanamycin or neomycin. Transformed primary colonies were easily recognized due to a different colony morphology. Replica filter plating, previously not obtained with mycoplasmas, was achieved using pNZ18 as a marker by incubating the replica filters with the cell side down on the new agar plates. These findings should greatly facilitate the genetic and functional analysis of A. laidlawii.
NOTCH1, NOTCH3, NOTCH4, and JAG2 protein levels in human endometrial cancer (2014)

The reduced amount of NOTCH4 and JAG2 proteins and the decreased level of mRNA coding Notch proteins, as reported in our previous studies, supports the notion that Notch pathway has rather tumor-suppressive than oncogenic role in human endometrial cancer cells. It suggests that Notch pathway activation is a potential therapeutic target.
A multi-branch monopole antenna for dual-band cellular applications (2003)

A monopole antenna with two branches, but still having one feed point, is proposed for the dual-band cellular applications. Simulation results of a dual-band antenna are presented. As shown in the results, the input impedances at the center of both bands are about 50 /spl Omega/. Therefore, an additional matching network is not necessary. This means there is no efficiency loss due to adding matching networks. The radiation patterns are basically omnidirectional. Although the GSM and DCS bands are used here, similar results can be obtained for the 900 MHz and 2.4 GHz ISM bands. The antenna can be made on a single-sided printed circuit board.
Pichia pastoris ‘just in time’ alternative respiration (2007)

Alternative oxidases (Aox or Aod) are present in the mitochondria of plants, fungi and many types of yeast. These enzymes transfer electrons from the ubiquinol pool directly to oxygen without contributing to the proton transfer across the mitochondrial membrane. Alternative oxidases are involved in stress responses, programmed cell death and maintenance of the cellular redox balance. The alternative oxidase gene of the methylotrophic yeast Pichia pastoris was isolated and cloned to study its regulation and the effects of deregulation of the alternative respiration by overexpression or disruption of the gene. Both disruption and overexpression had negative effects on the biomass yield; however, the growth rate and substrate uptake rate of the strain overexpressing the alternative oxidase were slightly increased. These effects were even more pronounced when higher glucose concentrations were used. The occurrence of free intracellular radicals and cell death phenomena was investigated using dihydrorhodamine 123 and the TUNEL test. The results suggest a major contribution of the alternative oxidase to P. pastoris cell viability. The negative effects of deregulated alternative respiration clearly indicated the importance of precise regulation of the alternative oxidase in this yeast.
RETINAL THICKNESS IN DIABETIC RETINOPATHY (2006)

Both measuring techniques yielded similar results when examining eyes of patients with diabetes, although absolute values differed. OCT seems to be more suitable in the clinical screening for macular edema due to its high sensitivity (>90%) with appropriate analysis parameters. The RTA is more prone to erroneous or missing thickness readings particularly under difficult measuring conditions.
A Common Neural Mechanism for Preventing and Terminating the Allocation of Attention (2012)

Much is known about the mechanisms by which attention is focused to facilitate perception, but little is known about what happens to attention after perception of the attended object is complete. One possibility is that the focus of attention passively fades. A second possibility is that attention is actively terminated after the completion of perception so that the brain can be prepared for the next target. The present study investigated this issue with event-related potentials in humans, focusing on the N2pc component (a neural measure of attentional deployment) and the Pd component (a neural measure of attentional suppression). We found that active suppression occurred both to prevent the allocation of attention to known distractors and to terminate attention after the perception of an attended object was complete. In addition, the neural measure of active suppression was correlated with a behavioral measure of trial-to-trial variations in the allocation of attention. Active suppression therefore appears to be a general-purpose mechanism that both prevents and terminates the allocation of attention.
Multi-View Video Plus Depth Representation and Coding (2007)

A study on the video plus depth representation for multi-view video sequences is presented. Such a 3D representation enables functionalities like 3D television and free viewpoint video. Compression is based on algorithms for multi-view video coding, which exploit statistical dependencies from both temporal and inter-view reference pictures for prediction of both color and depth data. Coding efficiency of prediction structures with and without inter-view reference pictures is analyzed for multi-view video plus depth data, reporting gains in luma PSNR of up to 0.5 dB for depth and 0.3 dB for color. The main benefit from using a multi-view video plus depth representation is that intermediate views can be easily rendered. Therefore the impact on image quality of rendered arbitrary intermediate views is investigated and analyzed in a second part, comparing compressed multi-view video plus depth data at different bit rates with the uncompressed original.
Derivation of Chondrogenically-Committed Cells from Human Embryonic Cells for Cartilage Tissue Regeneration (2008)

The direct chondrocytic commitment of FF-hESCs can be induced by morphogenetic factors from chondrocytes without EB formation and homogenous cartilage tissue can be formed in vitro and in vivo.
The Mammalian SIR2α Protein Has a Role in Embryogenesis and Gametogenesis (2002)

The yeast Sir2p protein has an essential role in maintaining telomeric and mating type genes in their transcriptionally inactive state. Mammalian cells have a very large proportion of their genome inactive and also contain seven genes that have regions of homology with the yeast sir2 gene. One of these mammalian genes, sir2alpha, is the presumptive mammalian homologue of the yeast sir2 gene. We set out to determine if sir2alpha plays a role in mammalian gene silencing by creating a strain of mice carrying a null allele of sir2alpha. Animals carrying two null alleles of sir2alpha were smaller than normal at birth, and most died during the early postnatal period. In an outbred background, the sir2alpha null animals often survived to adulthood, but both sexes were sterile. We found no evidence for failure of gene silencing in sir2alpha null animals, suggesting that either SIR2alpha has a different role in mammals than it does in Saccharomyces cerevisiae or that its role in gene silencing in confined to a small subset of mammalian genes. The phenotype of the sir2alpha null animals suggests that the SIR2alpha protein is essential for normal embryogenesis and for normal reproduction in both sexes.