gebhart/patrepeval huggingface dataset:
A Comprehensive Description of Hypoxia-inducible Factor 2α Inhibitorsas Anticancer Agents: A Mini-review (2022)

Targeting the tumor microenvironment is a promising strategy to prevent metastasis, overcome acquired drug resistance, and improve the therapeutic effect. Hypoxia is one of the characteristics of the tumor microenvironment, which is mainly regulated by hypoxia-inducible factors. Hypoxia-inducible factors (HIFs) including HIF-1α, HIF-2α, and HIF-3α, of which HIF-2α has assumed a more important role in tumor hypoxia environment. It has been demonstrated that HIF-2α plays an important role in tumor diseases, including renal cell carcinoma, breast cancer, non-small cell lung cancer, and gastric cancer, among others. Therefore, targeting HIF-2α has become one of the important strategies for treating cancers. HIF-2α inhibitors can be divided into two categories: specific inhibitors and non-specific inhibitors. The former includes synthetic monomer compounds and traditional Chinese medicine extracts. In this review, we summarized, classified, and discussed current research on the structure, structure-activity relationship (SAR), and pharmacology of HIF-2α inhibitors, which is helpful to the rational design of effective drugs for various types of malignant tumors.
Multi-Modality Multi-Task Recurrent Neural Network for Online Action Detection (2018)

Online action detection is a brand new challenge and plays a critical role in visual surveillance analytics. It goes one step further than a conventional action recognition task, which recognizes human actions from well-segmented clips. Online action detection is desired to identify the action type and localize action positions on the fly from the untrimmed stream data. In this paper, we propose a multi-modality multi-task recurrent neural network, which incorporates both RGB and Skeleton networks. We design different temporal modeling networks to capture specific characteristics from various modalities. Then, a deep long short-term memory subnetwork is utilized effectively to capture the complex long-range temporal dynamics, naturally avoiding the conventional sliding window design and thus ensuring high computational efficiency. Constrained by a multi-task objective function in the training phase, this network achieves superior detection performance and is capable of automatically localizing the start and end points of actions more accurately. Furthermore, embedding subtask of regression provides the ability to forecast the action prior to its occurrence. We evaluate the proposed method and several other methods in action detection and forecasting on the online action detection data set and gaming action data set datasets. Experimental results demonstrate that our model achieves the state-of-the-art performance on both tasks.
Selecting T-Cell Subsets for Adoptive T-Cell Therapy to Optimize Potency and Persistence (2013)

Abstract Adoptive T-cell therapy with tumor-reactive T cells is emerging as a highly effective strategy for eliminating even the most advanced chemotherapy refractory malignancies. Endogenous T cells specific for tumor-associated antigens can sometimes be isolated and expanded from the patient’s blood or tumor infiltrate, or more expeditiously can be engineered by gene transfer to express a T-cell receptor specific for a tumor associated MHC/peptide complex or a synthetic chimeric antigen receptor (CAR) specific for a tumor associated cell surface molecule. The remarkable regression of advanced acute lymphocytic leukemia and lymphoma in patients treated with T cells engineered to express CD19-specific CARs illustrates the potential for this approach to transform clinical care. Therapeutic activity is variable in individual patients, however, and this appears to correlate with the ability of transferred, tumor-reactive T cells to persist and proliferate in vivo, and to retain effector function. These attributes may reflect both the qualities of the T cells that are isolated or engineered for therapy, and the local tumor microenvironment that may contain regulatory T cells; cells that express ligands that engage inhibitor receptors on effector T cells or cytokines that inhibit effector T-cell proliferation. The CD4+ and CD8+ T cell pools in normal individuals contain a variety of naïve, memory, and regulatory T-cell subsets that differ in epigenetic, transcriptional, and functional properties. Because most clinical protocols have used polyclonal peripheral blood mononuclear cells as recipients for CAR gene transfer, the composition of T-cell products that are being administered is highly variable, particularly when the T cells are obtained from cancer patients that have received prior cytotoxic chemotherapy that can skew the phenotypic composition of the peripheral T-cell pool. As a consequence, transferring tumor-targeting receptors into polyclonal unselected cell populations provides poor control over the cellular composition of the final T-cell product, which may in part explain the marked differences in efficacy and toxicity that have been observed in the clinic, and may complicate regulatory approval of these novel therapies. Methods to derive T cells from distinct naïve and memory T-cell subsets have been developed, enabling the rapid production of therapeutic T cells of uniform composition. The results of preclinical studies that illustrate the improved potency of defined T-cell products that are engineered with tumor-specific CARs, and the clinical implementation of this approach in B-cell malignancies will be presented. Disclosures: Riddell: Cell Medica: Consultancy, Membership on an entity’s Board of Directors or advisory committees; ZetaRx: Consultancy.
Pyrophosphate-Selective Fluorescent Chemosensor at Physiological pH:  Formation of a Unique Excimer upon Addition of Pyrophosphate (2007)

We report a new fluorescent chemosensor that displays an excellent selectivity for pyrophosphate over adenosine triphosphate or phosphate in 100% aqueous solution. A unique fluorescent change was observed upon formation of a 2+2 excimer of the chemosensor.
Acylthiourea, Acylurea, and Acylguanidine Derivatives with Potent Hedgehog Inhibiting Activity (2012)

The Smoothened (Smo) receptor is the major transducer of the Hedgehog (Hh) signaling pathway. On the basis of the structure of the acylthiourea Smo antagonist (MRT-10), a number of different series of analogous compounds were prepared by ligand-based structural optimization. The acylthioureas, originally identified as actives, were converted into the corresponding acylureas or acylguanidines. In each series, similar structural trends delivered potent compounds with IC(50) values in the nanomolar range with respect to the inhibition of the Hh signaling pathway in various cell-based assays and of BODIPY-cyclopamine binding to human Smo. The similarity of their biological activities, in spite of discrete structural differences, may reveal the existence of hydrogen-bonding interactions between the ligands and the receptor pocket. Biological potency of compounds 61, 72, and 86 (MRT-83) were comparable to those of the clinical candidate GDC-0449. These findings suggest that these original molecules will help delineate Smo and Hh functions and can be developed as potential anticancer agents.
The ENDOTRIAL Study: A Spontaneous, Open-Label, Randomized, Multicenter, Crossover Study on the Efficacy of Sildenafil, Tadalafil, and Vardenafil in the Treatment of Erectile Dysfunction (2009)

An overall equivalence was demonstrated in the subjective perception of treatment benefits for all the PDE5i tested. However, sildenafil, in a dose-dependent manner, was the unique PDE5i able to ameliorate some of the penile flow parameters within the 8-week treatment period. These findings should be interpreted conservatively because of the observational nature of the study.
Track changing by use of the phase response of microspheres and resonators (1998)

A microsphere or resonator that is side coupled to an incident optical beam induces a phase response in the beam. In the so-called overcoupled regime, the amplitude of the incident beam remains unmodulated, whereas the phase goes through a shift of p at resonance. This shift is insensitive to the details of the coupling geometry or the resonant mode. In conjunction with an interferometer, the phase response can be used to switch the beam between two well-defined outputs, thus offering a robust means of deploying microspheres and other microresonators in practical photonic devices.
Identification of sequence segments forming the alpha-bungarotoxin binding sites on two nicotinic acetylcholine receptor alpha subunits from the avian brain (1991)

The relationship between neuronal alpha-bungarotoxin binding proteins (alpha BGTBPs) and nicotinic acetylcholine receptor function in the brain of higher vertebrates has remained controversial for over a decade. Recently, the cDNAs for two homologous putative ligand binding subunits, designated alpha BGTBP alpha 1 and alpha BGTBP alpha 2, have been isolated on the basis of their homology to the N terminus of an alpha BGTBP purified from chick brain. In the present study, a panel of overlapping synthetic peptides corresponding to the complete chick brain alpha BGTBP alpha 1 subunit and residues 166-215 of the alpha BGTBP alpha 2 subunits were tested for their ability to bind 125I-alpha BGT. The sequence segments corresponding to alpha BGTBP alpha 1-(181-200) and alpha BGTBP alpha 2-(181-200) were found to consistently and specifically bind 125I-alpha BGT. The ability of these peptides to bind alpha BGT was significantly decreased by reduction and alkylation of the Cys residues at positions 190/191, whereas oxidation had little effect on alpha BGT binding activity. The relative affinities for alpha BGT of the peptide sequences alpha BGTBP alpha 1-(181-200) and alpha BGTBP alpha 2-(181-200) were compared with those of peptides corresponding to the sequence segments Torpedo alpha 1-(181-200) and chick muscle alpha 1-(179-198). In competition assays, the IC50 for alpha BGTBP alpha 1-(181-200) was 20-fold higher than that obtained for the other peptides (approximately 2 versus 40 microM). These results indicate that alpha BGTBP alpha 1 and alpha BGTBP alpha 2 are ligand binding subunits able to bind alpha BGT at sites homologous with nAChR alpha subunits and that these subunits may confer differential ligand binding properties on the two alpha BGTBP subtypes of which they are components.
Low-frequency magnetic noise in magnetic tunnel junctions (2004)

We studied low-frequency noise in $\mathrm{NiFe}\ensuremath{-}{\mathrm{Al}}_{2}{\mathrm{O}}_{3}\ensuremath{-}\mathrm{NiFe}$ based magnetic tunnel junctions (MTJ's) with and without a hard-axis bias field. The $1/f$ noise is observed to be magnetic-field dependent and reduced with the application of hard-axis bias fields, attributed to thermally activated magnetization fluctuations in the magnetic electrodes. A linear dependence of noise on derivative of magnetoresistance has been observed, and the magnetic-field noise for MTJ sensing elements is defined and evaluated to be as low as 60 nT $\ensuremath{\mu}\mathrm{m}/{\mathrm{Hz}}^{1/2}.$
A tilted grating interferometer for full vector field differential x-ray phase contrast tomography (2011)

We report on a setup for differential x-ray phase-contrast imaging and tomography, that measures the full 2D phase-gradient information. The setup uses a simple one-dimensional x-ray grating interferometer, in which the grating structures of the interferometer are oriented at a tilt angle with respect to the sample rotation axis. In such a configuration, the differential phase images from opposing tomography projections can be combined to yield both components of the gradient vector. We show how the refractive index distribution as well as its x, y, and z gradient components can be reconstructed directly from the recorded projection data. The method can equally well be applied at conventional x-ray tube sources, to analyzer based x-ray imaging or neutron imaging. It is demonstrated with measurements of an x-ray phantom and a rat brain using synchrotron radiation.
Matched metal die compression molded structural random fiber sheet molding compound flywheel. [Patent application] (1980)

A flywheel is described that is useful for energy storage in a hybrid vehicle automotive power system or in some stationary applications. The flywheel has a body of essentially planar isotropic high strength structural random fiber sheet molding compound (SMC-R). The flywheel may be economically produced by a matched metal die compression molding process. The flywheel makes energy intensive efficient use of a fiber/resin composite while having a shape designed by theory assuming planar isotropy.
Phase Conjugate Mirror With Gain Based On Brillouin Scattering (1988)

We describe a new type of phase-conjugate mirror based on Brillouin enhanced four-wave mixing that has many attractive features distinguishing it from previous types of phase-conjugate mirrors. Chief among these features are its high reflectivity, ease of alignment, and its insensitivity to aberrations on the pump waves. Both theoretical and experimental results are presented.
Improvement of Characteristic Temperature in In<sub>0.81</sub>Ga<sub>0.19</sub>As/InGaAsP Multiple Quantum Well Laser Operating at 1.74 µm for Laser Monitor (1999)

InGaAs/InGaAsP compressively strained quantum well lasers operating at 1.74 µm have been fabricated with thin carrier blocking layers sandwiching the active layer for carrier confinement. A laser characteristic temperature ( T 0 ) of 85 K was obtained, which is the highest value ever reported in InGaAs/InGaAsP lasers in this wavelength range.
Doc2Img: A New Approach to Vectorization of Documents (2018)

Vector space representations of text have increased in popularity and are used in various text classification problems. We present Doc2Img, a new approach to create document vectors that improves upon existing approaches such as Word2Vec and Doc2Vec in capturing similarities between words within a document and the differences across documents. We apply this new vector space representation to the problem of deriving the sensor requirements of apps (for smartphones and IoT devices) by learning a classification model using document vectors. We show that this learned model outperforms existing vector space representations (Word2Vec and Doc2Vec) by more than 10%. Further, this model can predict with an average accuracy of 75% and greater than 85% on the top-20 sensor requirements for 300 different applications.
Development of a Novel Backbone Cyclic Peptide Inhibitor of the Innate Immune TLR/IL1R Signaling Protein MyD88 (2018)

MyD88 is a cytoplasmic adaptor protein that plays a central role in signaling downstream of the TLRs and the IL1R superfamily. We previously demonstrated that MyD88 plays a critical role in EAE, the murine model of multiple sclerosis, and showed that the MyD88 BB-loop decoy peptide RDVLPGT ameliorates EAE. We now designed and screened a library of backbone cyclized peptides based on the linear BB loop peptide, to identify a metabolically stable inhibitor of MyD88 that retains the binding properties of the linear peptide. We identified a novel cyclic peptide protein mimetic that inhibits inflammatory responses to TLR ligands, and NFκB activation in response to IL-1 activation. The inhibitor, c(MyD 4-4), is metabolically stable in comparison to the linear peptide, blocks MyD88 in a specific manner, and inhibits MyD88 function by preventing MyD88 dimerization. Finally, treatment of mice with c(MyD 4-4) reduced the severity of clinical disease in the murine EAE model of multiple sclerosis. Thus, modulation of MyD88-dependent signaling using c(MyD 4-4) is a potential therapeutic strategy to lower innate immune inflammation in autoimmune CNS disease.
Osteoblast-Derived Extracellular Vesicles Are Biological Tools for the Delivery of Active Molecules to Bone (2017)

Extracellular vesicles (EVs) are newly appreciated regulators of tissue homeostasis and a means of intercellular communication. Reports have investigated the role of EVs and their cargoes in cellular regulation and have tried to fine-tune their biotechnological use, but to date very little is known on their function in bone biology. To investigate the relevance of EV-mediated communication between bone cells, we isolated EVs from primary mouse osteoblasts and assessed membrane integrity, size, and structure by transmission electron microscopy (TEM) and fluorescence-activated cell sorting (FACS). EVs actively shuttled loaded fluorochromes to osteoblasts, monocytes, and endothelial cells. Moreover, osteoblast EVs contained mRNAs shared with donor cells. Osteoblasts are known to regulate osteoclastogenesis, osteoclast survival, and osteoclast function by the pro-osteoclastic cytokine, receptor activator of nuclear factor κ-B ligand (Rankl). Osteoblast EVs were enriched in Rankl, which increased after PTH treatment. These EVs were biologically active, supporting osteoclast survival. EVs isolated from rankl<sup>-/-</sup> osteoblasts lost this pro-osteoclastic function, indicating its Rankl-dependence. They integrated ex vivo into murine calvariae, and EV-shuttled fluorochromes were quickly taken up by the bone upon in vivo EV systemic administration. Rankl<sup>-/-</sup> mice lack the osteoclast lineage and are negative for its specific marker tartrate-resistant acid phosphatase (TRAcP). Treatment of rankl<sup>-/-</sup> mice with wild-type osteoblast EVs induced the appearance of TRAcP-positive cells in an EV density-dependent manner. Finally, osteoblast EVs internalized and shuttled anti-osteoclast drugs (zoledronate and dasatinib), inhibiting osteoclast activity in vitro and in vivo. We conclude that osteoblast EVs are involved in intercellular communication between bone cells, contribute to the Rankl pro-osteoclastic effect, and shuttle anti-osteoclast drugs, representing a potential means of targeted therapeutic delivery. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
Identification of the anti-adhesive site buried within the heparin-binding domain of fibronectin. (1997)

We recently found that heparin-binding domain 2 (Hep 2) of fibronectin (FN) exhibits cryptic anti-adhesive activity. In order to locate the anti-adhesive site, a number of synthetic peptides which represents the primary structure of the Hep 2 domain were characterized as to their ability to decrease the adhesion of A375SM melanoma cells to FN substrate. Only one peptide (T-E-A-T-I-T-G-L-E-P-G-T-E-Y-T-I-Y-V-I-A-L, residues 1835-1855) (peptide III14-2), which is situated between the previously identified adhesive sites, FN-C/H-I and II, decreased the cell adhesion to FN. Assaying of the anti-adhesive activities of sub-peptides showed that the hydrophobic moiety of peptide III14-2 (underlined sequence) seems to be indispensable for the anti-adhesive activity. These results suggest that anti-adhesive activity is closely associated with the sequence, Y-T-I-V-I-A-L, that is usually buried within the Hep 2 domain structure because of its hydrophobic nature.
Synthetic aperture radar interferometry (2000)

Synthetic aperture radar interferometry is an imaging technique for measuring the topography of a surface, its changes over time, and other changes in the detailed characteristic of the surface. By exploiting the phase of the coherent radar signal, interferometry has transformed radar remote sensing from a largely interpretive science to a quantitative tool, with applications in cartography, geodesy, land cover characterization, and natural hazards. This paper reviews the techniques of interferometry, systems and limitations, and applications in a rapidly growing area of science and engineering.
Mapping of polypeptides encoded by the Epstein-Barr virus genome in productive infection. (1982)

Over 30 viral-specified polypeptides are translated in vitro from RNA of cells productively infected with Epstein-Barr virus (EBV). The polypeptides map to sites in EBV DNA by hybrid selection. Almost all of the polypeptides are reactive with EBV immune human serum. Several of the polypeptides are part of the early antigen complex. Two others are likely to be major structural components of the virus. Genes encoding persistent early and late polypeptides are intermixed through most of the EBV genome.
Instantaneous thickness measurement of multilayer films by single-shot angle-resolved spectral reflectometry (2019)

In this Letter, we describe a new, to the best of our knowledge, concept of angle-resolved spectral reflectometry with a pixelated polarizing camera for determination of the thickness of each film layer in multilayer films. We can measure the changes in the phase and amplitude of p- and s-polarized light over a broad spectral range and a wide incident angle at a time. The proposed method is verified by measuring a sample of multilayer film and comparing our measurement results with an ellipsometer. The comparison results show that our proposed technique enables real-time inspection of multilayer films with high precision.
High-resolution quantitative whole-breast ultrasound: in vivo application using frequency-domain waveform tomography (2015)

Ultrasound tomography is a promising modality for breast imaging. Many current ultrasound tomography imaging algorithms are based on ray theory and assume a homogeneous background which is inaccurate for complex heterogeneous regions. They fail when the size of lesions approaches the wavelength of ultrasound used. Therefore, to accurately image small lesions, wave theory must be used in ultrasound imaging algorithms to properly handle the heterogeneous nature of breast tissue and the diffraction effects that it induces. Using frequency-domain ultrasound waveform tomography, we present sound speed reconstructions of both a tissue-mimicking breast phantom and <i>in vivo </i>data sets. Significant improvements in contrast and resolution are made upon the previous ray based methods. Where it might have been difficult to differentiate a high sound speed tumor from bulk breast parenchyma using ray based methods, waveform tomography improves the shape and margins of a tumor to help more accurately differentiate it from the bulk breast tissue. Waveform tomography sound speed imaging might improve the ability of finding lesions in very dense tissues, a difficult environment for mammography. By comparing the sound speed images produced by waveform tomography to MRI, we see that the complex structures in waveform tomography are consistent with those in MRI. The robustness of the method is established by reconstructing data acquired by two different ultrasound tomography prototypes.
3-Hydroxyphthaloyl-β-Lactoglobulin. I. Optimization of Production and Comparison with other Compounds Considered for Chemoprophylaxis of Mucosally Transmitted Human Immunodeficiency Virus Type 1 (1997)

Modification of the major bovine whey protein, β-lactoglobulin (β-LG) by 3-hydroxyphthalic anhydride (3HP) leads to the generation of a potent inhibitor of infection by human immunodeficiency virus (HIV) types 1 and 2, designated 3HP-β-LG. 3HP-β-LG also has antiviral activity against herpesviruses, albeit at concentrations exceeding those required for inhibition of HIV-1 infection. The topical application of 3HP-β-LG to decrease the rate of sexual transmission of HIV and other sexually transmitted viruses worldwide is being considered. Results presented here: (i) define the conditions for chemical modification of β-LG by 3HP, resulting in 3HP-β-LG with optimum anti-HIV-1 activity; (ii) show that β-LG, prior to chemical modification, or 3HP-β-LG can be exposed to the elevated temperatures used to pasteurize milk without adversely affecting anti-HIV-1 activity; (iii) provide evidence that 3HP-β-LG is a more potent anti-HIV-1 compound than sulphated polysaccharides, other candidate compounds considered as prophylactic agents to prevent sexual transmission of HIV-1; and (iv) confirm that the primary target for 3HP-β-LG is CD4, although binding to the HIV-1 envelope protein gp120 was also observed and contributed to the antiviral activity of 3HP-β-LG.