gebhart/patrepeval huggingface dataset:
Met5-enkephalin-Arg6-Phe7, an endogenous neuropeptide, binds to multiple opioid and nonopioid sites in rat brain (1997)

Receptor binding properties of the naturally occurring opioid heptapeptide MERF were studied in rat brain membrane preparations using tritium-labeled derivative of the peptide with 40 Ci/mmol specific radioactivity. Binding assays were performed in the presence of broad-spectrum peptidase inhibitors at 0 degree C. Under these conditions, the equilibrium binding was achieved in 30-40 min, and approximately 90% of the applied radioligand remained unchanged as determined by HPLC analysis. The apparent affinity (Kd value) of [3H]Met-enkephalin-Arg6-Phe7, calculated from saturation binding data, was 10.2 +/- 2.5 nM, and the maximal number (Bmax) of the heptapeptide binding sites was found to be 468 +/- 43 fmol/mg protein. About half the sites represent nonopioid sites because the Bmax was only 255 +/- 30 fmol/mg, when the nonspecific binding was measured with 1 microM naloxone. The rank order potencies of the examined compounds revealed that the opioid component of [3H]Met-enkephalin-Arg6-Phe7 recognition site are probably not mu and certainly not kappa 1 sites, whereas these sites are characterized by a kappa 2-like binding profile. Considering the discrepancies between rat and frog brain found in the affinity of some compounds, including naltrindole and norbinaltorphimine, the presence of a novel, MERF-selective "heptapeptide" binding site in rat brain membranes is also suggested. A number of the heterologous competition curves could be described by a high-affinity stereospecific component and a substantially lower-affinity binding element, which could completely be displaced with several peptide ligands such as Met5-enkephalin, dynorphin(1-13), and unlabeled MERF but not by other compounds such as [D-Ala2-(Me)Phe4-Gly5-ol]enkephalin, morphine, or naloxone. [3H]Met-enkephalin-Arg6-Phe7 binding can also be inhibited by FMRF-amide analogs and sigma receptor ligands, such as (+)N-allyl-normetazocine and haloperidol, although with moderate affinity. It is concluded that the stereospecific high-affinity binding is of opioid in character, whereas the residual sites characterized with their lower affinity are naloxone-insensitive nonopioid sites.
CCLXIX.—Imino-aryl ethers. Part III. The molecular rearrangement of N-phenylbenziminophenyl ether (1925)

A. W. Chapman, J. Chem. Soc., Trans., 1925, 127, 1992 DOI: 10.1039/CT9252701992
Role of Insulin in Development of Cancer Cachexia in Nongrowing Sarcoma-Bearing Mice: Special Reference to Muscle Wasting (1987)

This study evaluated whether altered insulin metabolism is a key factor behind weight loss during sarcoma growth in nongrowing mice (C57BL/6J). Fasted sarcoma-bearing mice had decreased blood glucose concentrations but unchanged levels of insulin, compared with those in pair-weighed and freely fed controls. During refeeding, insulin levels were inappropriately low for the degree of glycemia in sarcoma-bearing mice compared with those of pair-weighed and freely fed controls. Injections ip of glucose to tumor-bearing animals resulted in insulin levels comparable to postabsorptive values in healthy control animals, indicating that hypoinsulinemia in freely eating tumor-bearing animals was due to a reduced glycemic sensitivity for pancreatic insulin release. Insulin supplementation at doses [4 IU/100 g (body wt)] that increase body fat in normal animals could not protect the tumor-bearing host from progressive loss of body fat or lean tissues. Exogenous insulin in excess of endogenous insulin production did not stimulate tumor growth. Nitrogen and RNA-DNA content were significantly decreased in the quadriceps muscle of tumor-bearing mice. This reduction was independent of altered insulin levels and could not be prevented by exogenous insulin. The depressed capacity of protein synthesis in extensor digitorum longus (EDL) muscle could be entirely attributed to the state of malnutrition in tumor-bearing animals. The sensitivity and responsiveness of protein synthesis in EDL muscles to insulin were normal in tumor-bearing mice, regardless of whether exogenous insulin exerted its effect in vivo or in vitro. This study confirms insulin resistance for glucose metabolism in an experimental sarcoma animal model. Such changes are concluded to be secondary to anorexia and necessary to counteract hypoglycemia. In non-growing sarcoma-bearing mice, malnutrition and anorexia account entirely for depressed muscle protein synthesis, which is not explained by insulin resistance at the translational level. Insulin metabolism is not a key factor behind progression of wasting in sarcoma-bearing mice, but anorexia is.
Effect of Dosing Schedule on Pharmacokinetics of Alpha Interferon and Anti-Alpha Interferon Neutralizing Antibody in Mice (2001)

The influences of dosing time and dosing schedule on the plasma alpha interferon (IFN-alpha) concentration and the production of anti-IFN-alpha neutralizing antibodies were investigated in ICR male mice adapted to cycles of 12 h of light and 12 h of dark. In mice pretreated with IFN-alpha for 21 days, the plasma IFN-alpha concentrations were significantly lower than those in control mice (P < 0.01). The clearance of IFN-alpha and its volume of distribution obtained at steady state were significantly higher in the animals with IFN-alpha pretreatment than in the mice without IFN-alpha pretreatment. The area under the concentration-time curve and the mean residence time of IFN-alpha were significantly smaller in IFN-alpha-pretreated animals than in control animals. The plasma IFN-alpha levels (measured 2 h after dosing) were significantly lower in mice treated daily with IFN-alpha, while the anti-IFN-alpha neutralizing antibody levels (measured 24 h after dosing) were significantly increased on days 15 and 21 of treatment. Plasma IFN-alpha levels were significantly decreased in association with the production of anti-IFN-alpha neutralizing antibodies in mice treated with IFN-alpha daily at either 0900 or 2100 h. By contrast, the plasma IFN-alpha levels (measured 2 h after dosing) remained stable in mice treated with IFN-alpha at 0900 h on alternate days, while they were significantly lower after 21 days of treatment in mice treated with IFN-alpha at 2100 h on alternate days. These changes were associated with a significant increase in the levels of anti-IFN-alpha neutralizing antibodies in the latter group. The present findings suggest that an appropriate dosing schedule and/or dosing time for IFN-alpha may reduce the level of production of anti-IFN-alpha neutralizing antibodies in experimental and clinical situations.
Dynamical structure of water: Low-frequency Raman scattering from a disordered network and aggregates (1990)

Low-frequency inelastic light scattering of water is observed from a temperature equal to 80 down to −20 °C in the supercooled regime. For energies higher than 3 cm−1 it is shown that the major part of the light scattering is Raman scattering. A broadband with a maximum at 50 cm−1 is interpreted as scattering from transverse acoustic modes of a disordered network. A weaker scattering which shifts towards the Rayleigh line when the temperature decreases is well explained by Raman scattering from the oscillations of water molecule aggregates which grow when the temperature decreases.
Group recommendation (2009)

We study the problem of group recommendation. Recommendation is an important information exploration paradigm that retrieves interesting items for users based on their profiles and past activities. Single user recommendation has received significant attention in the past due to its extensive use in Amazon and Netflix. How to recommend to a group of users who may or may not share similar tastes, however, is still an open problem. The need for group recommendation arises in many scenarios: a movie for friends to watch together, a travel destination for a family to spend a holiday break, and a good restaurant for colleagues to have a working lunch. Intuitively, items that are ideal for recommendation to a group may be quite different from those for individual members. In this paper, we analyze the desiderata of group recommendation and propose a formal semantics that accounts for both item relevance to a group and disagreements among group members. We design and implement algorithms for efficiently computing group recommendations. We evaluate our group recommendation method through a comprehensive user study conducted on Amazon Mechanical Turk and demonstrate that incorporating disagreements is critical to the effectiveness of group recommendation. We further evaluate the efficiency and scalability of our algorithms on the MovieLens data set with 10M ratings.
Reversal of Cisplatin Resistance with Amphotericin B in a Non‐small Cell Lung Cancer Cell Line (1991)

The potentiation of anticancer agents by non-anticancer drugs is one of the possible strategies for overcoming cellular resistance to chemotherapy. In order to overcome cis-diamminedichloroplatinum(II) (CDDP) resistance, we evaluated the sensitizing effect on CDDP-induced cytotoxicity of various non-anticancer agents which might alter membrane transport, by means of a colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. Drugs which have previously been demonstrated to modify multidrug resistance did not show a sensitizing effect to cisplatin. Only amphotericin B (AmB) selectively conquered CDDP resistance in the CDDP-resistant cell line. A drug accumulation study done by the atomic absorption method demonstrated that the accumulation of CDDP in the resistant cell line recovered to the level of the parental cell line after treatment with AmB. Thus, AmB might overcome CDDP resistance by increasing the accumulation of CDDP.
Functional Similarities Among Genes Regulated by Oct4 in Human Mesenchymal and Embryonic Stem Cells (2007)

OCT4 is a master transcriptional regulator, which mediates pluripotency in ESCs through inhibition of tissue-specific and promotion of stem cell-specific genes. Suppression of OCT4, along with other regulators of pluripotency, such as SOX2 and NANOG, has been correlated with cell-fate specification and lineage-specific differentiation. Recent reports have shown the expression of OCT4 in adult MSCs but have not ascribed functional homology with ESCs. MSCs are mesoderm-derived cells, primarily resident in adult bone marrow, that undergo lineage-specific differentiation to generate specialized cells such as stroma, fat, bone, and cartilage. We have previously demonstrated the plasticity of MSCs through their ability to generate neuronal cells. Here, we show that OCT4 provides similar regulatory circuitries in human MSCs and ESCs, using chromatin immunoprecipitation-DNA selection and ligation technology and loss-of-function studies. MSCs were found to express the embryonic transcription factors OCT4, NANOG, and SOX2. In addition, OCT4 was found to (a) target similar genes in MSCs and ESCs, (b) promote the expression of MSC-specific genes, and (c) regulate MSC cell cycle progression. The results suggest similar regulatory mechanisms for OCT4 in MSCs and ESCs and have implications regarding MSC plasticity. Disclosure of potential conflicts of interest is found at the end of this article.
Ta-based interface ohmic contacts to AlGaN/GaN heterostructures (2001)

Al/Ti based metallization is commonly used for ohmic contacts to n-GaN and related compounds. We have previously reported an ohmic contact scheme specially designed for AlGaN/GaN heterostructure field-effect transistors (HFETs) [D. Qiao et al., Appl. Phys. Lett. 74, 2652 (1999)]. This scheme, referred to as the “advancing interface” contact, takes advantage of the interfacial reactions between the metal layers and the AlGaN barrier layer in the HFET structure. These reactions consume a portion of the barrier, thus facilitating carrier tunneling from the source/drain regions to the channel region. The advancing interface approach has led to consistently low contact resistance on Al0.25Ga0.75N/GaN HFETs. There are two drawbacks of the Al/Ti based advancing interface scheme, (i) it requires a capping layer for the ohmic formation annealing since Ti is too reactive and is easily oxidized when annealing is performed in pure N2 or even in forming gas, and (ii) the atomic number of Al and that of Ti are too low to yield efficient backscattered electron emission for e-beam lithographic alignment purposes. In this work, we investigated a Ta based advancing interface contact scheme for the HFET structures. We found that the presence of Ta in this ohmic scheme leads to (1) a specific contact resistivity as low as 5×10−7 Ω cm2, (2) efficient electron emission for e-beam lithographic alignment, and (3) elimination of the capping layer for the ohmic annealing.
Imaging Progesterone Receptor in Breast Tumors: Synthesis and Receptor Binding Affinity of Fluoroalkyl-Substituted Analogues of Tanaproget (2010)

The progesterone receptor (PR) is estrogen regulated, and PR levels in breast tumors can be used to predict the success of endocrine therapies targeting the estrogen receptor (ER). Tanaproget is a nonsteroidal progestin agonist with very high PR binding affinity and excellent in vivo potency. When appropriately radiolabeled, it might be used to image PR-positive breast tumors noninvasively by positron emission tomography (PET). We describe the synthesis and PR binding affinities of a series of fluoroalkyl-substituted 6-aryl-1,4-dihydrobenzo[d][1,3]oxazine-2-thiones, analogues of Tanaproget. Some of these compounds have subnanomolar binding affinities, higher than that of either Tanaproget itself or the high affinity PR ligand R5020. Structure-binding affinity relationships can be rationalized by molecular modeling of ligand complexes with PR, and the enantioselectivity of binding has been predicted. These compounds are being further evaluated as potential diagnostic PET imaging agents for breast cancer, and enantiomerically pure materials of defined stereochemistry are being prepared.
Long-term operation of a sealed waveguide CO2 laser (1981)

A mass spectrometer has been utilized to study the gas composition during operation of a CO2 laser using a BeO waveguide. The results indicate that the use of a drying agent to absorb water vapor has allowed us to achieve lifetimes in excess of 5000 h in sealed waveguide lasers.
An Investigation of the Relationship Between Acoustic Emission, Vibration, Noise, and Cavitation Structures on a Kaplan Turbine (2007)

Abstract The goal of the study was to explain the relationship between different acoustic signals and visual appearance of cavitation. Measurements of acoustic emission, vibration, and noise were performed on a Kaplan turbine model, with only two blades, in a cavitating condition. Since a model with only two blades was used, most of the side effects were eliminated, and it was concluded that the cavitation itself is the source of the recorded signal. Results showed an interesting relationship between the extent of the cavitation and the recorded data from sensors. At a decreasing cavitation number, the recorded amplitudes from all measurements first rose, experienced a local maximum, then fell to a local minimum, and finally rose again. The cavitation was also visually observed. It was concluded from the measurements that there are distinct correlations between acoustic emission, vibration, and noise on one side and the topology, extent, and type of cavitation structures on the other side. A physical explanation for the phenomenon was introduced and included in a semi-empirical model that links the visual appearance of cavitation on the blade of the turbine to the generated noise and vibration.
High-user-density digital cellular mobile radio systems (1985)

Digital cellular mobile radio systems are described having partially overlapping cells that are based on road configurations, and in which the energy is radiated along the road from approximately street lamp elevations. One proposed system uses propagation frequencies in the vicinity of 900 MHz, employs adaptive differential pulse code modulation at 32 kbit/s and a minimum shift keying modem enabling a channel spacing of 25 kHz. One example of system performance shows that, for clusters of ten cells along a six-lane highway, the signal/interference ratio is 20 dB, the probability of error is 10
 -3
, and the channel SNR is 10.8 dB. Given an allocated mobile radio bandwidth of 20 MHz, the system can support 80 users per cell. If the vehicles are travelling at 88 km/h (55 miles/h) and 10% of the drivers make a telephone call, the cell length is 4.8 km (3 miles), and the cochannel distance is 48 km (30 miles). In our deliberations we made comparisons with conventional analogue FM systems, and showed that they have approximately half the user density capacity of the new system. A digital microcellular mobile radio systems employing 60 GHz is also considered. The bit rate per segment of road was found to be vast, e. g. 100 Mbit/s per 100 m of road. This system is capable of providing portable communications to large numbers of pedestrians and drivers in congested city streets. Because of the configuration of the proposed cell structure, shadow fading is conjectured to have very little impact on system performance.
Structure-guided design fine-tunes pharmacokinetics, tolerability, and antitumor profile of multispecific frizzled antibodies (2019)

Aberrant activation of Wnt/β-catenin signaling occurs frequently in cancer. However, therapeutic targeting of this pathway is complicated by the role of Wnt in stem cell maintenance and tissue homeostasis. Here, we evaluated antibodies blocking 6 of the 10 human Wnt/Frizzled (FZD) receptors as potential therapeutics. Crystal structures revealed a common binding site for these monoclonal antibodies (mAbs) on FZD, blocking the interaction with the Wnt palmitoleic acid moiety. However, these mAbs displayed gastrointestinal toxicity or poor plasma exposure in vivo. Structure-guided engineering was used to refine the binding of each mAb for FZD receptors, resulting in antibody variants with improved in vivo tolerability and developability. Importantly, the lead variant mAb significantly inhibited tumor growth in the HPAF-II pancreatic tumor xenograft model. Taken together, our data demonstrate that anti-FZD cancer therapeutic antibodies with broad specificity can be fine-tuned to navigate in vivo exposure and tolerability while driving therapeutic efficacy.
Modeling of Purification Operations in Biotechnology: Enabling Process Development, Optimization, and Scale‐Up (2007)

Process modeling involves the use of a set of mathematical equations to represent key physical phenomena involved in the process. An appropriately validated model can be used to predict process behavior with limited experimental data, identify critical ranges for process variables, and guide further process development. Although process modeling is extensively used in the chemical process industries, it has not been widely used in purification unit operations in biotechnology. Recent FDA guidelines encourage the use of process modeling during process development, along with multivariate statistical methods, detailed risk assessment, and other quantifiers of uncertainty. This paper will review recent advances in the modeling of key downstream unit operations: chromatography, filtration, and centrifugation. The focus will be on the application of modeling for industrial applications. Relevant papers presented at a session on this topic at the recent American Chemical Society National Meeting in San Francisco will also be reviewed.
Engineers evaluate submersible pumps in North Sea field (1982)

Experimentation with several different electric submersible pump designs and installations in the UK's Montrose field, whose oil production has been hindered by increasing water cuts and highly deviated wells turning up marginal amounts of sand is described. Gas lift is a possible alternative to the pumps since there is platform space for facilities to be installed, and sufficient gas production during the major part of the field life. Submersible pumps as artificial lifts require a continuing operating cost to pull and regularly replace failed units.
Toward Cleavable Metabolic/pH Sensing “Double Agents” Hyperpolarized by NMR Signal Amplification by Reversible Exchange (2018)

We show the simultaneous generation of hyperpolarized <sup>13</sup> C-labeled acetate and <sup>15</sup> N-labeled imidazole following spin-relay of hyperpolarization and hydrolysis of the acetyl moiety on 1-<sup>13</sup> C-<sup>15</sup> N<sub>2</sub> -acetylimidazole. Using SABRE-SHEATH (Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei), transfer of spin order occurs from parahydrogen to acetylimidazole <sup>15</sup> N atoms and the acetyl <sup>13</sup> C site (≈263-fold enhancement), giving rise to relatively long hyperpolarization lifetimes at 0.3 T (T<sub>1</sub> ≈52 s and ≈149 s for <sup>13</sup> C and <sup>15</sup> N, respectively). Immediately following polarization transfer, the <sup>13</sup> C-labeled acetyl group is hydrolytically cleaved to produce hyperpolarized <sup>13</sup> C-acetate/acetic acid (≈140-fold enhancement) and <sup>15</sup> N-imidazole (≈180-fold enhancement), the former with a <sup>13</sup> C T<sub>1</sub> of ≈14 s at 0.3 T. Straightforward synthetic routes, efficient spin-relay of SABRE hyperpolarization, and facile bond cleavage open a door to the cheap and rapid generation of long-lived hyperpolarized states within a wide range of molecular targets, including biologically relevant carboxylic acid derivatives, for metabolic and pH imaging.
Applications of Azo-Based Probes for Imaging Retinal Hypoxia (2015)

We report the design and synthesis of an activatable molecular imaging probe to detect hypoxia in mouse models of retinal vascular diseases. Hypoxia of the retina has been associated with the initiation and progression of blinding retinal vascular diseases including age-related macular degeneration, diabetic retinopathy, and retinopathy of prematurity. In vivo retinal imaging of hypoxia may be useful for early detection and timely treatment of retinal diseases. To achieve this goal, we synthesized HYPOX-3, a near-infrared (NIR) imaging agent coupled to a dark quencher, Black Hole Quencher 3 (BHQ3), which has been previously reported to contain a hypoxia-sensitive cleavable azo-bond. HYPOX-3 was cleaved in hypoxic retinal cell culture and animal models, enabling detection of hypoxia with high signal-to-noise ratios without acute toxicity. HYPOX-3 fluorescences in hypoxic cells and tissues and was undetectable under normoxia. These imaging agents are promising candidates for imaging retinal hypoxia in preclinical disease models and patients.