gebhart/patrepeval huggingface dataset:
The Value of Home-Grown Companies (1993)

Over the past decade we have been involved in more than fifty economic development projects in cities and towns across the Pioneer Valley. These have ranged from the revitalization of older industrial areas in Springfield, the development of incubator facilities in Chicopee, the reuse of the Waverly Mill in Adams to the siting of a new industrial park in Deerfield. In each case we are almost always questioned about how a community could encourage the next Pratt and Whitney Digital or BMW plant to come to our region. Upon hearing the question, we point out that there are only 1200 major plant location decisions made in a typical year and that there are 20,000 industrial development commissions chasing these companies. We also point out, that all things considered, home-grown, home-owned businesses bring a comprehensive set of assets to a community that are most often of greater value than, for example, a branch plant of a multinational company. We base our perspective on the following six points:
Pure oestrogen antagonists for the treatment of advanced breast cancer (2006)

For more than 30 years, tamoxifen has been the drug of choice in treating patients with oestrogen receptor (ER)-positive breast tumours. However, research has endeavoured to develop agents that match and improve the clinical efficacy of tamoxifen, but lack its partial agonist effects. The first 'pure' oestrogen antagonist was developed in 1987; from this, an even more potent derivative was developed for clinical use, known as fulvestrant (ICI 182,780, 'Faslodex'). Mechanistic studies have shown that fulvestrant possesses high ER-binding affinity and has multiple effects on ER signalling: it blocks dimerisation and nuclear localisation of the ER, reduces cellular levels of ER and blocks ER-mediated gene transcription. Unlike anti-oestrogens chemically related to tamoxifen, fulvestrant also helps circumvent resistance to tamoxifen. There are extensive data to support the lack of partial agonist effects of fulvestrant and, importantly, its lack of cross-resistance with tamoxifen. In phase III studies in patients with locally advanced or metastatic breast cancer, fulvestrant was at least as effective as anastrozole in patients with tamoxifen-resistant tumours, was effective in the first-line setting and was also well tolerated. These data are supported by experience from the compassionate use of fulvestrant in more heavily pretreated patients. Further studies are now underway to determine the best strategy for sequencing oestrogen endocrine therapies and to optimise dosing regimens offulvestrant. At present, and for the foreseeable future, fulvestrant is the only oestrogen antagonist with no agonistic effects licensed for the treatment of advanced breast cancer in postmenopausal women. Other similar oestrogen antagonists are undergoing research and development, with a few currently being evaluated in phase II trials.
Contour Interaction and Visual Resolution: Contralateral Effects (1963)

Detection of the gap in a four-position Landolt C presented to one eye is impaired by critically spaced surrounding bars seen only by the other eye. The intensity and spatial extent of this contralateral contour interaction match those obtained ipsilaterally. These results indicate that the neural site for this loss of visual information is supraretinal.
Bacterium-host cell interactions at the cellular level: fluorescent labeling of bacteria and analysis of short-term bacterium-phagocyte interaction by flow cytometry (1994)

Flow cytometry is a potentially powerful tool for analyzing the interactions of facultative intracellular bacteria and macrophages on a cellular level, particularly when fluorochromes are used to label the bacteria. We labeled Listeria monocytogenes and Salmonella typhimurium with a lipophilic dye, PKH-2, and used flow cytometry to investigate phagocytosis by J774A.1 cells and short-term bacterial survival. Labeled and unlabeled bacteria were identical in terms of viability, growth kinetics, and survival within macrophages, although recovery per macrophage was much greater for L. monocytogenes than for S. typhimurium. Using L. monocytogenes as a prototypical facultative intracellular bacterium, we estimated bacterial survival during phagocytosis on the basis of linear fluorescence measurements of infected J774A.1 cells and recovery of L. monocytogenes from sorted cells. The lower percentage of surviving L. monocytogenes in macrophages containing higher bacterial loads indicated the accumulation of nonviable bacteria within phagocytes. Removal of the external source of viable bacteria by washes and gentamicin treatment reduced the percentage of surviving intracellular L. monocytogenes to a baseline level, and all baseline levels were similar, regardless of bacterial load. Listeria enrichment recoveries, derived from individually sorted J774A.1 cells, demonstrated the heterogeneity of macrophages in intracellular bacterial survival, especially within heavily infected cells. These results indicated that survival of L. monocytogenes was dependent on the adaptations of a small fraction of bacteria within a population of macrophages which permit intracellular growth.
Isavuconazole: Pharmacology, Pharmacodynamics, and Current Clinical Experience with a New Triazole Antifungal Agent (2015)

Coinciding with the continually increasing population of immunocompromised patients worldwide, the incidence of invasive fungal infections has grown over the past 4 decades. Unfortunately, infections caused by both yeasts such as Candida and molds such as Aspergillus or Mucorales remain associated with unacceptably high morbidity and mortality. In addition, the available antifungals with proven efficacy in the treatment of these infections remain severely limited. Although previously available second-generation triazole antifungals have significantly expanded the spectrum of the triazole antifungal class, these agents are laden with shortcomings in their safety profiles as well as formulation and pharmacokinetic challenges. Isavuconazole, administered as the prodrug isavuconazonium, is the latest second-generation triazole antifungal to receive U.S. Food and Drug Administration approval. Approved for the treatment of both invasive aspergillosis and invasive mucormycosis, and currently under investigation for the treatment of candidemia and invasive candidiasis, isavuconazole may have therapeutic advantages over its predecessors. With clinically relevant antifungal potency against a broad range of yeasts, dimorphic fungi, and molds, isavuconazole has a spectrum of activity reminiscent of the polyene amphotericin B. Moreover, clinical experience thus far has revealed isavuconazole to be associated with fewer toxicities than voriconazole, even when administered without therapeutic drug monitoring. These characteristics, in an agent available in both a highly bioavailable oral and a β-cyclodextrin-free intravenous formulation, will likely make isavuconazole a welcome addition to the triazole class of antifungals.
Synthesis and Evaluation of (17α,20<i>Z</i>)-21-(4-Substituted-phenyl)-19-norpregna-1,3,5(10),20-tetraene-3,17β-diols as Ligands for the Estrogen Receptor-α Hormone Binding Domain:  Comparison with 20<i>E</i>-Isomers (2005)

As part of our ongoing program to develop probes for the hormone binding domain of the estrogen receptor-alpha (ERalpha), we prepared and evaluated a series of 17alpha,Z-(4-substituted-phenyl)vinyl estradiol derivatives. The results indicated that the relative binding affinities (RBAs) at 25 degrees C for the new compounds were significant (RBA = 9-57) although less than that of estradiol (RBA = 100) or of the parent unsubstituted phenylvinyl estradiol (RBA = 66). All of the Z-compounds were full agonists in the uterotrophic assay, indicating that the ligands formed estrogen-like complexes with the estrogen receptor-alpha hormone binding domain (ERalpha-HBD). Comparison of corresponding Z- and E-4-substituted phenylvinyl ligands complexed with the ERalpha-HBD indicated small but significant differences in binding modes that may account for the differing trends seen in the structure-activity relationships for the two series.
Study of a three-dimensional seismic detection system (1964)

Abstract As part of the VELA program for evaluating systems for detecting underground nuclear events, a three-dimensional seismic array was instrumented and operated for over a year. Three seismometers spaced 1,320 ft apart were clamped to casing in each of five abandoned oil wells near Tryon, Oklahoma, and their outputs individually recorded on magnetic tape and conventional oscillograms. By time-shifting and compositing to achieve optimum signal coherence, signal-to-noise improvement factors somewhat greater than (rad)n times the ratio for a surface detector were obtained in the signal spectrum from 4 to 10 cps, with lower improvement factors in the 1- to 4-cps range. Studies of the nature of the site noise and its attenuation characteristics with depth are presented together with autocorrelation, power-spectrum, and coherence plots. To a depth of approximately 1,300 ft, the noise decay is exponential and characteristic of the fundamental Rayleigh mode. Below this depth the pattern is more complex and may be representative of higher mode Rayleigh and body waves. Expressions were derived for the theoretical comparison of the relative directional response of two- and three-dimensional arrays.
Tuning the Photophysical Properties of Metal-Free Room Temperature Organic Phosphors via Compositional Variations in Bromobenzaldehyde/Dibromobenzene Mixed Crystals (2014)

Spurred by several recent discoveries and a broad and largely unexplored design space, purely organic phosphorescent materials are starting to garner interest for potential applications in organic optoelectronics and sensors. One particularly promising class of purely organic phosphor is the family consisting of bromobenzaldehyde emitters doped into crystals of dibromobenzene hosts. These stand out by featuring bright, robust, and color-tunable room temperature phosphorescence. However, despite these attractive qualities, the mixed crystal motif defining these materials puts complex demands on crystal packing, chemical structure, and sample preparation in ways that are not yet well understood. Here we report a detailed study on these materials to optimize emission efficiency and fine-tune color. Overall, data suggest that achieving efficient inclusion of the emitter into the host crystal is critical to optimizing quantum efficiency. Phosphorescent emission from the mixed crystals is polarized, indicating that bromobenzaldehyde guest is ordered in the dibromobenzene host crystal. While host compounds tolerate a surprising variety of emitter sizes, both oversized and undersized, maximum quantum efficiency is reached when emitters and hosts are identically sized and the former is present at 1–10 wt % of total solids. The optimum quantum efficiency for these systems appears, empirically, to be in the range of 45–55%. To fine-tune emission color, altering the halogen substitution of the emitter molecule affords sequential 5–30 nm changes to emission maxima within the green region. The relatively minor impact these alterations have on the overall chemical structure affords color tuning with minimal detriment to mixing efficiency.
AMP-activated Protein Kinase β Subunit Tethers α and γ Subunits via Its C-terminal Sequence (186–270) (2005)

AMP-activated protein kinase (AMPK) is an important metabolic stress-sensing protein kinase responsible for regulating metabolism in response to changing energy demand and nutrient supply. Mammalian AMPK is a stable alphabetagamma heterotrimer comprising a catalytic alpha and two non-catalytic subunits, beta and gamma. The beta subunit targets AMPK to membranes via an N-terminal myristoyl group and to glycogen via a mid-molecule glycogen-binding domain. Here we find that the conserved C-terminal 85-residue sequence of the beta subunit, beta1-(186-270), is sufficient to form an active AMP-dependent heterotrimer alpha1beta1-(186-270)-gamma1, whereas the 25-residue beta1 C-terminal (246-270) sequence is sufficient to bind gamma1, gamma2, or gamma3 but not the alpha subunit. Deletion of the beta C-terminal Ile-270 precludes betagamma association in the absence of the alpha subunit, but the presence of the alpha subunit or substitution of Ile-270 with Ala or Glu restores betagamma binding. Truncation of the alpha subunit reveals that beta1 binding requires the alpha1-(313-473) sequence. The conserved C-terminal 85-residue sequence of the beta subunit (90% between beta1 and beta2) is the primary alphagamma binding sequence responsible for the formation of the AMPK alphabetagamma heterotrimer.
Solvent Extraction and Its Applications on Ore Processing and Recovery of Metals: Classical Approach (2016)

Solvent extraction is widely employed in a variety of industries for both the upgrading and purification of a range of elements and chemicals. The technology is used in applications as diverse as ore processing, pharmaceuticals, agriculture, industrial chemicals, petrochemicals, food industry, purification of base metals and refining of precious metals. This review deals with the basics of solvent extraction technique and discusses in detail its applications in several fields focusing on ore processing and recovery of important metals from economic and industrial point of view.
Design of Lane-Keeping Control with Steering Torque Input for a Lane-Keeping Support System (2001)

<div class="htmlview paragraph">This paper describes the method used to design the basic control algorithm of a lane-keeping support system that is intended to assist the driver's steering action. Lane-keeping control has been designed with steering torque as the control input without providing a minor loop for the steering angle. This approach was taken in order to achieve an optimum balance of lane-keeping control, ease of steering intervention by the driver and robustness. The servo control system was designed on the basis of <i>H</i><sub>2</sub> control theory. Robustness against disturbances, vehicle nonlinearity and parameter variation was confirmed by <i>μ</i> - analysis. The results of computer simulations and driving tests have confirmed that the control system designed with this method provides the intended performance.</div>
Beneficial Effects of the Bioflavonoids Curcumin and Quercetin on Early Function in Cadaveric Renal Transplantation: A Randomized Placebo Controlled Trial (2005)

Bioflavonoid therapy improved early graft function. Acute rejection and neurotoxicity were lowest in the high dose group. These bioflavonoids improve early outcomes in cadaveric renal transplantation, possibly through HO-1 induction.
PROTEINS AND ANIONIC POLYSACCHARIDES AS STABILIZERS OP 0/W EMULSIONS (1985)

ABSTRACT The possibilities of stabilizing emulsions by means of proteins and polysaccharides have been discussed. It is shown that the use of anionic polysaccharides makes it possible to increase considerably the stability of protein-containing emulsions. The developed methods of stabilizing emulsions by means of anionic polysaccharides are protein-universal and useful for the preparation of emulsions based on phases of different polarity. The use of these methods allows to avoid the use of low-molecular surfactants for the preparation of protein-containing C/W emulsions.
Binocular co‐ordination of human horizontal saccadic eye movements. (1988)

1. The binocular co-ordination of human horizontal saccades was analysed for the first time systematically over the full oculomotor range with a precise and accurate scleral sensor coil technique. Effects of amplitude (1.25-80 deg), direction (adduction vs. abduction and centrifugal vs. centripetal) and eccentricity (symmetrical about primary or between primary and secondary positions) were systematically investigated in three subjects). 2. To minimize extraneous effects of stimulus presentation on the programming of saccades, subjects were instructed to voluntarily change their gaze between two continuously visible targets. These were positioned on an iso-vergence locus, and thus contained no stimulus for disjunctive eye movements. 3. Under these conditions the amplitudes of the primary saccades of the two eyes were remarkably accurate; undershooting of the target by about 0.5 deg (independent of amplitude in the range 10-70 deg) was typical. This finding contrasts with the undershooting by about 10% described in the literature as characteristic for other stimulus conditions. 4. Saccadic peak velocities saturated at a mean asymptotic level of 502 +/- 32 (S.D.) deg/s for saccades of 40 deg and larger. The duration was linearly related to amplitude for saccades up to 50 deg; for saccades of larger sizes the duration increased progressively more steeply. Skewness values (acceleration time as a fraction of total saccadic duration) decreased from about 0.45 for saccades up to 10 deg to about 0.20 for saccades of 50 deg and larger. 5. Binocular saccades showed an abduction-adduction asymmetry and were not well yoked dynamically. The saccades of the abducting eye consistently had a larger size, a higher peak velocity, a shorter duration and were more skewed than the concomitant adducting saccades of the fellow eye. As a result, the eyes diverged transiently by as much as 3 deg during horizontal saccades. 6. Saccades also showed a marked centrifugal-centripetal asymmetry. Peak velocities of saccades towards the primary position were about 10% higher than peak velocities of corresponding centrifugal saccades. 7. These directional asymmetries were the main source of variability in the pool of saccades. In comparison, intra- and intersubject variability was minor in our sample. 8. Post-saccadic drift consisted of a vergence and a version component. The vergence component of this drift was a continuation of the vergence movement occurring during saccades. The version component, generally smaller than the vergence component, was directed towards the target position.(ABSTRACT TRUNCATED AT 400 WORDS)
Shell structure and strengthening of superconducting pair correlation in nanoclusters (2006)

The existence of shell structure and the accompanying high degeneracy of electronic levels leads to the possibility of strong superconducting pairing in metallic nanoclusters with $N\ensuremath{\sim}{10}^{2}--{10}^{3}$ delocalized electrons. The most favorable cases correspond to (a) ``magic'' clusters with strongly degenerate highest occupied and lowest unoccupied shells and a relatively small energy spacing between them as well as to (b) clusters with slightly incomplete shells and small Jahn-Teller splitting. It is shown that realistic sets of parameters lead to very high values of ${T}_{c}$ as well as to a strong alteration of the energy spectrum. The impact of fluctuations is analyzed. Spectroscopic experiments aimed at detecting the presence of pair correlations are proposed. The pairing should also manifest itself via odd-even effects in cluster spectra, similar to the case in nuclei.
Quantitative Femtosecond Charge Transfer Dynamics at Organic/Electrode Interfaces Studied by Core‐Hole Clock Spectroscopy (2014)

Organic semiconductor materials have important applications in organic electronics and other novel hybrid devices. In these devices, the transport of charge carriers across the interfaces between organic molecules and electrodes plays an important role in determining the device performance. Charge transfer dynamics at the organic/electrode interface usually occurs at the several femtoseconds timescale, and quantitative charge transfer dynamics data can been inferred using synchrotron-based core-hole clock (CHC) spectroscopy. In this research news, we have reviewed recent progress in the applications of CHC spectroscopy on the quantitative characterization of charge transfer dynamics at organic/electrode interfaces. By examining charge transfer dynamics at different types of interface, from weakly interacting van der Waals-type interfaces to interfaces with strong covalent bonds, we discuss a few factors that have been found to affect the charge transfer dynamics. We also review the application of CHC spectroscopy to quantify through-bonds and through-space charge transport in organic molecules.
Activity of Lambda-Exonuclease on Surface-Attached Oligonucleotide Detected by Acoustic Wave Device and Radiochemical Labeling (2008)

Abstract Single-strand 25-mer oligonucleotides have been attached to the surface of a 9-MHz acoustic wave sensor incorporated into a flow-through configuration. This was achieved by an online interaction of the biotinylated probe with chemisorbed neutravidin. Duplex formation with complementary 25-mer was monitored by acoustic wave detection in real time. Regeneration of the probe-modified surface was achieved using online introduction of λ-exonuclease, an enzyme that digests a single strand of double-stranded DNA beginning with the 5′ end, cleaving single nucleotides as it progresses. Thus, with the 5′ end of the probe strand remaining inaccessible because of the biotin-neutravidin linkage, the target strand was successfully removed by enzymatic digestion. The results of the acoustic wave work are correlated with analogous experiments involving oligonucleotides labeled with 32P. Keywords: Acoustic wave devicebiosensors λ-exonucleaseflow-through formatnucleic acid 32P labelingsensor regeneration The authors are grateful to the Natural Sciences and Engineering Research Council of Canada for support of this work. Also, we thank Jon Ellis of the Institute of Biomaterials and Biomedical Engineering of the University of Toronto for very helpful discussions regarding the physics of acoustic wave propagation and assistance in the preparation of the manuscript. Notes Note. Additions of labeled F2 are given in bold type. a Labeled F2 is designated F2∗. Conditions are A: F2 (39 pmol), exo (90 min); B: F2 (735 pmol), exo (90 min); C: F2 (750 pmol), exo (15 min); D: F2 (1490 pmol), exo (15) min.
Expression and Regulation of Corticotropin-Releasing Factor Receptor Type 2β in Developing and Mature Mouse Skeletal Muscle (2010)

Corticotropin-releasing factor receptor type 2 (CRFR2) is highly expressed in skeletal muscle (SM) tissue where it is suggested to inhibit interactions between insulin signaling pathway components affecting whole-body glucose homeostasis. However, little is known about factors regulating SM CRFR2 expression. Here, we demonstrate the exclusive expression of CRFR2, and not CRFR1, in mature SM tissue using RT-PCR and ribonuclease protection assays and report a differential expression of CRF receptors during C2C12 myogenic differentiation. Whereas C2C12 myoblasts exclusively express CRFR1, the C2C12 myotubes solely express CRFR2. Using cAMP luciferase assays and calcium mobilization measurements, we further demonstrate the functionality of these differentially expressed receptors. Using luciferase reporter assays we show a differential activation of CRFR promoters during myogenic differentiation. Transfections with different fragments of the 5'-flanking region of the mCRFR2β gene fused to a luciferase reporter gene show a promoter-dependent expression of the reporter gene and reveal the importance of the myocyte enhancer factor 2 consensus sequence located at the 3'-proximal region of CRFR2β promoter. Furthermore, we demonstrate that CRFR2 gene transcription in the mature mouse is stimulated by both high-fat diet and chronic variable stress conditions. Performing a whole-genome expression microarray analysis of SM tissues obtained from CRFR2-null mice or wild-type littermates revealed a robust reduction in retinol-binding protein 4 expression levels, an adipokine whose serum levels are elevated in insulin-resistant states. In correlation with the SM CRFR2β levels, the SM retinol-binding protein 4 levels were also elevated in mice subjected to high-fat diet and chronic variable stress conditions. The current findings further position the SM CRFR2 pathways as a relevant physiological system that may affect the known reciprocal relationship between psychological and physiological challenges and the metabolic syndrome.