gebhart/patrepeval huggingface dataset:
Tripartite steroid hormone receptor pharmacology: interaction with multiple effector sites as a basis for the cell- and promoter-specific action of these hormones. (1996)

The selective action that steroid hormones and the hormones for the other nuclear receptors have in different tissues and on different responses is well known. In fact, this recognized selectivity forms the basis for major efforts, currently underway in the pharmaceutical industry and at universities, toward the development of new, synthetic hormones whose profile of desired activities is optimized for specific therapeutic and preventative applications. This commentary will examine the pharmacological mechanisms that underlie this selectivity. The study of steroid hormone pharmacology poses particular challenges. In viva, many steroids have pleiotropic activity, displaying a variety of effects in different tissues. Even in cell-based in vitro systems, attempts to investigate the molecular basis for steroid hormone action and the selectivity of this action are confounded by the fact that the genomic responses elicited by these ligands can be both primary and secondary (Le. cascade) responses. In the latter situation, the correlation between molecular interaction and response is complex and indirect; this makes it difficult to clearly determine what interactions define the pharmacological parameters of potency and bio-
Predominant Expression of Mutant EGFR (EGFRvIII) is Rare in Primary Glioblastomas (2004)

EGFR amplification is a frequent genetic alteration in primary (de novo) glioblastomas, and is often associated with structural alterations. Most common is variant III (EGFRvIII), which results from a non-random 801 bp in-frame deletion of exons 2 to 7 of the EGFR gene. We assessed amplification and overexpression of EGFRvIII and wild-type EGFR in 30 glioblastoma biopsies. Immunohistochemically, EGFR overexpression was observed in 20 (67%) of 30 glioblastomas. Eight (27%) cases also showed immunoreactivity to an EGFRvIII antibody. In 6 of these cases, the pattern of EGFR and EGFRvIII overexpression was compared in serial sections: In 4 cases, areas with immunoreactivity to EGFRvIII largely coincided with wild-type EGFR expression. In the other 2 cases, the areas immunoreactive to EGFRvIII were significantly less extensive than EGFR-positive areas. To assess whether EGFRvIII is predominantly amplified in tumors with concurrent wild-type EGFR amplification, we carried our real-time quantitative PCR using 2 sets of primers located in exon 2 and intron 15 of the EGFR gene. A > 5-fold ratio of relative copy numbers between intron 15 (present both in wild-type EGFR and EGFRvIII) and exon 2 (present only in wild-type EGFR, but missing in EGFRvIII) suggested predominant amplification of EGFRvIII in only 3 (10%) of 30 glioblastomas. The observation that intratumoral wild-type EGFR overexpression is often more extensive and that predominant amplification of EGFRvIII is a rare event would limit the effectiveness of therapeutic approaches based on selective targeting of EGFRvIII.
L-696,474, a novel cytochalasin as an inhibitor of HIV-1 protease. I. The producing organism and its fermentation. (1992)

A novel cytochalasin, L-696,474, (18-dehydroxy cytochalasin H) that inhibits HIV-1 protease was discovered in fermentations of a bark-inhabiting Ascomycete, Hypoxylon fragiforme. The product was first identified from extracts of an agar medium. Fermentation studies on a number of media indicated that the product can be made on several solid and liquid media. Optimum production was obtained from growth in a complex medium composed of glycerol, glucose, citrate, Ardamine, soybean meal, tomato paste, and inorganic salts. Other Hypoxylon spp., related species of Xylariales, and other fungi known to produce cytochalasins, were also surveyed for their ability to make L-696,474. Only one other Hypoxylon fragiforme isolate was found to make this novel cytochalasin; none of the other cultures surveyed made L-696,474 or any other compounds which inhibit HIV-1 protease.
Signaling by Phosphoinositide-3,4,5-Trisphosphate Through Proteins Containing Pleckstrin and Sec7 Homology Domains (1997)

Signal transmission by many cell surface receptors results in the activation of phosphoinositide (PI) 3-kinases that phosphorylate the 3' position of polyphosphoinositides. From a screen for mouse proteins that bind phosphoinositides, the protein GRP1was identified. GRP1 binds phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4, 5)P3] through a pleckstrin homology (PH) domain and displays a region of high sequence similarity to the yeast Sec7 protein. The PH domain of the closely related protein cytohesin-1, which, through its Sec7 homology domain, regulates integrin beta2 and catalyzes guanine nucleotide exchange of the small guanine nucleotide-binding protein ARF1, was also found to specifically bind PtdIns(3,4,5)P3. GRP1 and cytohesin-1 appear to connect receptor-activated PI 3-kinase signaling pathways with proteins that mediate biological responses such as cell adhesion and membrane trafficking.
Structural evidence for methionine at the reactive site of human alpha-1-proteinase inhibitor. (1978)

An unadecapeptide, obtained by papain digestion of denatured human alpha-1-proteinase inhibitor (alpha-1-PI), has been isolated and sequenced. The structure of this fragment overlaps with the NH2-terminal sequence of modified inhibitor (alpha-1-PI) prepared from dissociated complexes of alpha-1-PI with trypsin, chymotrypsin, and elastase. Furthermore, structural homology with the reactive centers of proteinase inhibitors from other sources is readily detectable. Methionine has been found to occupy the apparent P1 position in alpha-1-PI and the potential inactivation of the inhibitor by oxidation of this critical residue may be important in obtaining a biochemical link with the development of lung disease.
Nonenzymatic Browning in Liquid Model Systems of High Water Activity: Kinetics of Color Changes due to Caramelization of Various Single Sugars (1987)

ABSTRACT The kinetics of color changes due to caramelization of various single sugar solutions (fructose, xylose, glucose, maltose, lactose, and sucrose) of water activity adjusted to 0.90 (by adding NaCl) and heated at various temperatures (45–65°C) was studied. A zero‐order and a “mixed”‐order kinetic model were satisfactorily used to describe the rate of color formation. Fructose and xylose solutions browned much more rapidly than those of maltose, glucose, lactose or sucrose. Activation energies for color development of fructose and xylose were in the range 25–30 kcal/mole, while for lactose and maltose they were 35–48 kcal/mole. Lowering of pH inhibited caramelization browning of sugar solutions. The role of hydrolysis in the browning of heated sucrose solutions was studied.
Kinetics of sealing for transient electropores in isolated mammalian skeletal muscle cells (1999)

Permeabilization of the plasma membrane by electrical forces (electroporation) can be either transient or stable. Although the exact molecular mechanics have not yet been described, electroporation is believed to initiate primarily in the lipid bilayer. To better understand the kinetics of membrane permeabilization, we sought to determine the time constants for spontaneous transient pore sealing. By using isolated rat flexor digitorum brevis skeletal muscle cells and a two-compartment diffusion model, we found that pore sealing times (tau p) after transient electroporation were approximately 9 min. tau p was not significantly dependent on the imposed transmembrane potential. We also determined the transmembrane potential (delta Vm) thresholds necessary for transient and stable electroporation in the skeletal muscle cells. delta VmS ranging between 340 mV and 480 mV caused a transient influx of magnesium, indicating the existence of spontaneously sealing pores. An imposed delta Vm of 540 mV or greater led to complete equilibration of the intracellular and extracellular magnesium concentrations. This finding suggests that stable pores are created by the larger imposed transmembrane potentials. These results may be useful for understanding nerve and skeletal muscle injury after an electrical shock and for developing optimal strategies for accomplishing transient electroporation, particularly for gene transfection and cell transformation.
Further Structure−Activity Relationship Studies of Piperidine-Based Monoamine Transporter Inhibitors:  Effects of Piperidine Ring Stereochemistry on Potency. Identification of Norepinephrine Transporter Selective Ligands and Broad-Spectrum Transporter Inhibitors (2005)

4-(4-Chlorophenyl)piperidine analogues each bearing a thioacetamide side chain appendage similar to that found in the wake-promoting drug modafinil have been synthesized. The transporter inhibitory activity of both the cis and trans isomers of these 3,4-disubstituted piperidines in both their (+)- and (-)-enantiomeric forms was determined. These studies reveal that the (-)-cis analogues exhibit dopamine transporter/norepinephrine transporter (DAT/NET) selectivity as was previously reported for the (+)-trans analogues. On the other hand, the (-)-trans and the (+)-cis isomers show serotonin transporter (SERT) or SERT/NET selectivity. Among them, (+)-cis-5b shows a low nanomolar Ki for the NET with 39-fold and 321-fold lower potency at the DAT and SERT, respectively, thus making it a useful pharmacological research tool for exploring NET-associated behavioral signatures. On the other hand, several of the compounds described herein, such as (+)-trans-5c, show comparable activity at all three transporters. Because broad-spectrum transporter inhibitors have been hypothesized to exhibit a more rapid onset of action and/or a greater efficacy as antidepressant agents than those selective for SERT or SERT + NET, some of the present compounds will be valuable to study in animal models of depression.
Integration strategies for audio-visual speech processing: applied to text-dependent speaker recognition (2005)

In this paper, an in-depth analysis is undertaken into effective strategies for integrating the audio-visual speech modalities with respect to two major questions. Firstly, at what level should integration occur? Secondly, given a level of integration how should this integration be implemented? Our work is based around the well-known hidden Markov model (HMM) classifier framework for modeling speech. A novel framework for modeling the mismatch between train and test observation sets is proposed, so as to provide effective classifier combination performance between the acoustic and visual HMM classifiers. From this framework, it can be shown that strategies for combining independent classifiers, such as the weighted product or sum rules, naturally emerge depending on the influence of the mismatch. Based on the assumption that poor performance in most audio-visual speech processing applications can be attributed to train/test mismatches we propose that the main impetus of practical audio-visual integration is to dampen the independent errors, resulting from the mismatch, rather than trying to model any bimodal speech dependencies. To this end a strategy is recommended, based on theory and empirical evidence, using a hybrid between the weighted product and weighted sum rules in the presence of varying acoustic noise for the task of text-dependent speaker recognition.
2.5 Gb/s x 16-channel bidirectional WDM transmission system using bidirectional erbium-doped fiber amplifier based on spectrally interleaved synchronized etalon filters (1999)

The implemented a bidirectional erbium-doped fiber amplifier using two spectrally interleaved synchronized etalon filters. This amplifier was used to demonstrate 2.5 Gb/s/spl times/16 channel bidirectional wavelength-division-multiplexed (WDM) transmission over 160-km-long single mode fiber. No power penalty was observed in receiver sensitivity caused by relative intensity noise. In addition, we measured the performance of the concatenated amplifiers using a recirculating loop. The results show that it would be possible to use the proposed amplifier for the transmission of bidirectional WDM signals over seven amplifier spans (/spl sim/560 km) with a span loss of 20 dB.
3D Printed Quantum Dot Light-Emitting Diodes (2014)

Developing the ability to 3D print various classes of materials possessing distinct properties could enable the freeform generation of active electronics in unique functional, interwoven architectures. Achieving seamless integration of diverse materials with 3D printing is a significant challenge that requires overcoming discrepancies in material properties in addition to ensuring that all the materials are compatible with the 3D printing process. To date, 3D printing has been limited to specific plastics, passive conductors, and a few biological materials. Here, we show that diverse classes of materials can be 3D printed and fully integrated into device components with active properties. Specifically, we demonstrate the seamless interweaving of five different materials, including (1) emissive semiconducting inorganic nanoparticles, (2) an elastomeric matrix, (3) organic polymers as charge transport layers, (4) solid and liquid metal leads, and (5) a UV-adhesive transparent substrate layer. As a proof of concept for demonstrating the integrated functionality of these materials, we 3D printed quantum dot-based light-emitting diodes (QD-LEDs) that exhibit pure and tunable color emission properties. By further incorporating the 3D scanning of surface topologies, we demonstrate the ability to conformally print devices onto curvilinear surfaces, such as contact lenses. Finally, we show that novel architectures that are not easily accessed using standard microfabrication techniques can be constructed, by 3D printing a 2 × 2 × 2 cube of encapsulated LEDs, in which every component of the cube and electronics are 3D printed. Overall, these results suggest that 3D printing is more versatile than has been demonstrated to date and is capable of integrating many distinct classes of materials.
Deletion of the α-Arrestin Protein Txnip in Mice Promotes Adiposity and Adipogenesis While Preserving Insulin Sensitivity (2010)

Txnip deletion promotes adiposity in the face of high-fat caloric excess; however, loss of this alpha-arrestin protein simultaneously enhances insulin responsiveness in fat and skeletal muscle, revealing Txnip as a novel mediator of insulin resistance and a regulator of adipogenesis.
Slot-coupled microstrip antenna for broadbandcircular polarisation (1998)

Broadband circular polarisation (CP) operation of single-feed slot-coupled microstrip antennas is achieved using an inclined nonlinear coupling slot. This nonlinear slot, end-loaded with two V slots, significantly broadens the CP bandwidth to about 2.1 times that obtained using a simple inclined coupling slot for CP operation. Details of the antenna design are described, and experimental results of the CP performance are presented.
Disruption of Endothelial Cell Interactions with the Novel HU177 Cryptic Collagen Epitope Inhibits Angiogenesis (2007)

We provide evidence for a new functional cryptic regulatory element within collagen IV that regulates tumor angiogenesis. These findings suggest a novel and highly selective approach for regulating angiogenesis by targeting a non-cellular cryptic collagen epitope.
Cloning and expression of chicken erythrocyte transglutaminase. (1992)

We report the sequences of cDNAs encoding chicken erythrocyte transglutaminase (EC 2.3.2.13). The complete mRNA consists of 3345/3349 nucleotides and predicts a single open reading frame. Nine peptide sequences derived from partial digests of the isolated protein agreed with the corresponding translation of the open reading frame. Approximately 60% identities between the avian protein and three related mammalian enzymes were found. Chicken erythrocyte transglutaminase mRNA is most abundant in red blood cells and kidney, and it accumulates during erythroid cell differentiation.
Time-Reversal Division Multiple Access in Multi-Path Channels (2011)

Multi-path effect makes high speed broadband communications a very challenging task due to the severe inter-symbol interference (ISI). By concentrating energy in both spatial and temporal domains, time-reversal (TR) transmission technique provides a great potential of low-complexity energy-efficient communications. In this paper, we develop a new concept of time-reversal division multiple access (TRDMA) as a wireless channel access method based on its high-resolution spatial focusing effect. We propose to use TR structure in a multi-user downlink system over large delay spread channels, where the signals of different users are separated solely by TRDMA. Both the single-transmit-antenna scheme and its enhanced version with multiple-transmit-antenna are developed and evaluated in this paper. We investigate the system performance in terms of the effective SINR and the achievable sum rate of the multi-user system. It is shown in both analytical and simulation results that satisfying performances can be achieved in the proposed TRDMA multi-user downlink system.
Improved fabrication of zero-mode waveguides for single-molecule detection (2008)

Metallic subwavelength apertures can be used in epi-illumination fluorescence to achieve focal volume confinement. Because of the near field components inherent to small metallic structures, observation volumes are formed that are much smaller than the conventional diffraction limited volume attainable by high numerical aperture far field optics (circa a femtoliter). Observation volumes in the range of 10−4fl have been reported previously. Such apertures can be used for single-molecule detection at relatively high concentrations (up to 20μM) of fluorophores. Here, we present a novel fabrication of metallic subwavelength apertures in the visible range. Using a new electron beam lithography process, uniform arrays of such apertures can be manufactured efficiently in large numbers with diameters in the range of 60–100nm. The apertures were characterized by scanning electron microscopy, optical microscopy, focused ion beam cross sections/transmission electron microscopy, and fluorescence correlation spectroscopy measurements, which confirmed their geometry and optical confinement. Process throughput can be further increased using deep ultraviolet photolithography to replace electron beam lithography. This enables the production of aperture arrays in a high volume manufacturing environment.
Improved performance white LED (2005)

This paper describes work leading to the development of a new packaging method for white LEDs, called scattered photon extraction (SPE). Previous work by our group showed that the traditional placement of the phosphor close to the die negatively affects the overall luminous efficacy and lumen maintenance of phosphor-converted white LEDs. The new SPE method enables higher luminous efficacy by placing the phosphor at a remote location from the die and by shaping the lens surrounding the die to extract a significant portion of the back-transferred light before it is absorbed by packaging components. Although the remote phosphor concept is not new, SPE is the first method to demonstrate efficient extraction of back-transferred light and show over 60 percent improvement in light output and efficacy compared to similar commercial white LEDs. At low currents, the prototype white LEDs based on the SPE technique showed over 80 lumens per watt. The SPE concept was tried on two types of commercial packages and both showed similar improvements.
Assessing the significance of chromosomal aberrations in cancer: Methodology and application to glioma (2007)

Comprehensive knowledge of the genomic alterations that underlie cancer is a critical foundation for diagnostics, prognostics, and targeted therapeutics. Systematic efforts to analyze cancer genomes are underway, but the analysis is hampered by the lack of a statistical framework to distinguish meaningful events from random background aberrations. Here we describe a systematic method, called Genomic Identification of Significant Targets in Cancer (GISTIC), designed for analyzing chromosomal aberrations in cancer. We use it to study chromosomal aberrations in 141 gliomas and compare the results with two prior studies. Traditional methods highlight hundreds of altered regions with little concordance between studies. The new approach reveals a highly concordant picture involving approximately 35 significant events, including 16-18 broad events near chromosome-arm size and 16-21 focal events. Approximately half of these events correspond to known cancer-related genes, only some of which have been previously tied to glioma. We also show that superimposed broad and focal events may have different biological consequences. Specifically, gliomas with broad amplification of chromosome 7 have properties different from those with overlapping focalEGFR amplification: the broad events act in part through effects on MET and its ligand HGF and correlate with MET dependence in vitro. Our results support the feasibility and utility of systematic characterization of the cancer genome.
Tapping the power of text mining (2006)

Sifting through vast collections of unstructured or semistructured data beyond the reach of data mining tools, text mining tracks information sources, links isolated concepts in distant documents, maps relationships between activities, and helps answer questions.
The E1 functional epitope of the human interferon gamma is a nuclear targeting signal-like element. Mapping of the E1 epitope. (1991)

Eight neutralizing monoclonal antibodies (mAbs) directed against the human interferon gamma (HuIFN-gamma) that were classified in the E1 epitope group were mapped by the synthetic peptide approach. A set of 136 octapeptide homologs of the 143-residue primary sequence of the HuIFN-gamma, each one with a 7-residue sequence overlap with successive peptide, was synthesized. Based on the similar reactivity patterns of all the mAbs with this set of synthetic peptides, the E1 functional epitope was localized to residues 84-94 on the HuIFN-gamma. The epitope sequence is: Ser-Asn-Lys-Lys-Lys-Arg-Asp-Asp-Phe-Gln-Lys. The fact that eight independently isolated mAbs binding to the same domain can neutralize the HuIFN-gamma activity suggests that the E1 domain must be at or adjacent to a functional site. Within this domain is a sequence element, Lys-Lys-Lys-Arg, that resembles the nuclear location signals known to effect the intracellular transportation of a number of nuclear proteins, such as the large tumor antigen (T antigen) of simian virus 40 (SV40) and polyoma virus and steroid hormone receptors. This observation suggests that the HuIFN-gamma molecule and/or its complex with the receptor must function in the nucleus to effect transcription regulation that results in the various biological activities. The signal for that intracellular transportation must be provided by the HuIFN-gamma molecule.
Integrated polarization compensator for WDM waveguide demultiplexers (1999)

An integrated polarization compensator for wavelength-division-multiplexed waveguide demultiplexers is proposed and experimentally demonstrated. It is simple to fabricate, has many advantages over previously reported polarization compensation schemes, and is effective in both etched diffraction grating and arrayed waveguide grating based devices.
Complex Chemistry and Biology of Redox-Active Compounds, Commonly Known as SOD Mimics, Affect Their Therapeutic Effects (2014)

This Editorial has the intention to stress the complex chemistry and biology of redox-active compounds, regarded as SOD mimics. It further aims to caution the researchers of the importance of being up-to-date with the present knowledge on such compounds and their cellular redox biology when coming up with their conclusions, based on the particular species involved in their studies.