gebhart/patrepeval huggingface dataset:
Inhibition of Tyrosine Kinase Activity of the Epidermal Growth Factor (EGF) Receptor by a Truncated Receptor Form That Binds to EGF: Role for Interreceptor Interaction in Kinase Regulation (1989)

The tyrosine kinase activity of the epidermal growth factor (EGF) receptor is regulated by a truncated receptor of 100 kilodaltons (kDa) that contains the EGF-binding site but not the kinase domain. The inhibition of kinase is not due to competition for available EGF or for the kinase substrate-binding site. Chemical cross-linking studies suggest that the 100-kDa receptor may form a heterodimer with the intact EGF receptor. Structurally related receptor kinases, such as the platelet-derived growth factor receptor, the insulin receptor, and the Neu receptor, were not inhibited by the 100-kDa receptor. The results indicate that (i) the inhibition was specific for the EGF receptor, (ii) the kinase domain had little or no role in determining target specificity, and (iii) the regulation of kinase may be due to a specific interaction of the 100-kDa receptor with the ligand-binding domain of the EGF receptor kinase.
Discovery of peptide inhibitors targeting human programmed death 1 (PD-1) receptor (2016)

Blocking the interaction of human programmed death 1 (hPD-1) and its ligand hPD-L1 has been a promising immunotherapy in cancer treatment. In this paper, using a computational de novo peptide design method, we designed several hPD-1 binding peptides. The most potent peptide Ar5Y_4 showed a KD value of 1.38 ± 0.39 μM, comparable to the binding affinity of the cognate hPD-L1. A Surface Plasmon Resonance (SPR) competitive binding assay result indicated that Ar5Y_4 could inhibit the interaction of hPD-1/hPD-L1. Moreover, Ar5Y_4 could restore the function of Jurkat T cells which had been suppressed by stimulated HCT116 cells. Peptides described in this paper provide promising biologic candidates for cancer immunotherapy or diagnostics.
Combined Chemotherapy and Radiotherapy Compared with Radiotherapy Alone in Patients with Cancer of the Esophagus (1992)

Concurrent therapy with cisplatin and fluorouracil and radiation is superior to radiation therapy alone in patients with localized carcinoma of the esophagus, as measured by control of local tumors, distant metastases, and survival, but at the cost of increased side effects.
A push–pull approach to maximize vaccine efficacy: Abrogating suppression with an IL-13 inhibitor while augmenting help with granulocyte/macrophage colony-stimulating factor and CD40L (2002)

Although a role for CD4(+) helper cells in CD8(+) cytotoxic T lymphocyte (CTL) induction by vaccines is widely recognized, much less is known about a counterbalancing role of CD4(+) T cells in down-modulating this response, or about ways to optimize vaccine responses through abrogation of this negative regulatory mechanism. Here, we discovered a synergistic enhancement of vaccine-mediated CTL induction and protection by the relief of suppression through depletion of regulatory CD4(+) cells, including CD4(+) NKT cells, or blockade of IL-13 made by these cells, combined with the cytokine granulocyte/macrophage colony-stimulating factor and the costimulatory molecule CD40L. Indeed, in the absence of helper epitopes, granulocyte/macrophage colony-stimulating factor and the helper-mimetic molecule CD40L are not sufficient to replace help to induce CTL without abrogation of CD4(+) T cell-mediated suppression, suggesting a role for T cell help in overcoming suppression. The increased CTL induction translated to striking protection against viral infection by a vaccine by using this synergistic combined approach. These results argue for a push-pull approach to maximize vaccine efficacy, especially for HIV and cancer.
MUCOSAL IL-12 INHIBITS AIRWAY REACTIVITY TO METHACHOLINE AND RESPIRATORY FAILURE IN MURINE ASTHMA (2000)

The worldwide incidence, prevalence, and fatality rates from asthma are increasing despite currently available therapeutic modalities. Systemic administration of interleukin (IL)-12 has been shown to inhibit airway reactivity in murine models of asthma, but the required dosage is high and may be toxic. This study tested the hypothesis that IL-12 administered directly into the lungs is more effective in inhibiting airway reactivity than systemically administered IL-12, allowing lower doses to be used. A low dose (10 ng) of IL-12 was delivered either intratracheally (mucosal delivery) or intraperitoneally (systemic delivery) at the time of ragweed (RW) challenge in mice sensitized to RW. Basal airway resistance and airway reactivity to methacholine were measured 3 days after RW challenge. Compared to phosphate-buffered saline (PBS) challenge of RW sensitized mice, RW challenge increased basal resistance and the slope of the methacholine dose-response curve. Methacholine challenge of RW-challenged mice also induced premature respiratory failure (respiratory rate < 150/min, tidal volume < 0.15 mL) in some animals. Administration of mucosal or systemic IL-12 at the time of RW challenge decreased basal airway resistance. However, only mucosal IL-12 decreased airway reactivity and inhibited respiratory failure during methacholine challenge. These findings indicate that mucosal delivery of a low dose of IL-12 is more effective than systemic IL-12 in inhibiting airway reactivity and respiratory failure in a mouse model of asthma.
First Direct Imaging of Giant Pores of the Metal−Organic Framework MIL-101 (2005)

Here we report the first direct imaging of the giant pores distribution in the MIL-101 compound, which represents the largest porous MOF discovered up to now, with cage volumes up to ca. 20 600 Å3 and a record sorption capacity (SLangmuir ∼ 5900 ± 300 m2·g-1).
Calcium-dependent Epidermal Growth Factor Receptor Transactivation Mediates the Angiotensin II-induced Mitogen-activated Protein Kinase Activation in Vascular Smooth Muscle Cells (1998)

We have recently reported that angiotensin II (Ang II)-induced mitogen-activated protein kinase (MAPK) activation is mainly mediated by Ca2+-dependent activation of a protein tyrosine kinase through Gq-coupled Ang II type 1 receptor in cultured rat vascular smooth muscle cells (VSMC). In the present study, we found Ang II rapidly induced the tyrosine phosphorylation of the epidermal growth factor (EGF) receptor and its association with Shc and Grb2. These reactions were inhibited by the EGF receptor kinase inhibitor, AG1478. The Ang II-induced phosphorylation of the EGF receptor was mimicked by a Ca2+ ionophore and completely inhibited by an intracellular Ca2+ chelator. Thus, AG1478 abolished the MAPK activation induced by Ang II, a Ca2+ ionophore as well as EGF but not by a phorbol ester or platelet-derived growth factor-BB in the VSMC. Moreover, Ang II induced association of EGF receptor with catalytically active c-Src. This reaction was not affected by AG1478. These data indicate that Ang II induces Ca2+-dependent transactivation of the EGF receptor which serves as a scaffold for pre-activated c-Src and for downstream adaptors, leading to MAPK activation in VSMC.
Synthesis and radiopharmacology of O-(2-[18F]fluoroethyl)-L-tyrosine for tumor imaging. (1999)

The high in vivo stability of L-[18F]FET, its fast brain and tumor uptake kinetics, its low accumulation in nontumor tissue and its ease of synthesis strongly support further evaluation of L-[18F]FET as an amino acid tracer for cerebral and peripheral tumors.
Reloading and stability of polyacrylamide slab gels for automated DNA sequencing. (1994)

Current automated fluorescent instruments are all based on slab gels that are used once and then discarded. Practitioners of capillary gel electrophoresis often reuse their gels for multiple samples. As slab gels are made thinner to increase speed, the ability to reload new samples after each run will become more desirable. Techniques have previously been developed for reloading and stabilizing capillary gels. The application of these methods to slab gel electrophoresis is reported. Gels are shown to be reusable for at least four consecutive automated runs. The stability of various slab gel formulations and their ability to survive multiple loadings with sequencing samples are compared. Formamide-containing gels are shown to be superior to their urea counterparts. The potential that running buffer additives have for improving automated DNA sequencing is discussed. Residual template DNA in sequencing samples can produce gel instability, reduce resolution and decrease signal. These effects are examined.
SuperHapten: a comprehensive database for small immunogenic compounds (2006)

The immune system protects organisms from foreign proteins, peptide epitopes and a multitude of chemical compounds. Among these, haptens are small molecules, eliciting an immune response when conjugated with carrier molecules. Known haptens are xenobiotics or natural compounds, which can induce a number of autoimmune diseases like contact dermatitis or asthma. Furthermore, haptens are utilized in the development of biosensors, immunomodulators and new vaccines. Although hapten-induced allergies account for 6-10% of all adverse drug effects, the understanding of the correlation between structural and haptenic properties is rather fragmentary. We have developed a manually curated hapten database, SuperHapten, integrating information from literature and web resources. The current version of the database compiles 2D/3D structures, physicochemical properties and references for about 7500 haptens and 25,000 synonyms. The commercial availability is documented for about 6300 haptens and 450 related antibodies, enabling experimental approaches on cross-reactivity. The haptens are classified regarding their origin: pesticides, herbicides, insecticides, drugs, natural compounds, etc. Queries allow identification of haptens and associated antibodies according to functional class, carrier protein, chemical scaffold, composition or structural similarity. SuperHapten is available online at http://bioinformatics.charite.de/superhapten.
Taxanes for the Treatment of Metastatic Breast Cancer (2012)

Taxanes have remained a cornerstone of breast cancer treatment over the past three decades, improving the lives of patients with both early- and late-stage disease. The purpose of this review is to summarize the current role of taxanes, including an albumin-bound formulation that enhances delivery of paclitaxel to tumors, in the management of metastatic breast cancer (MBC). Since the introduction of Cremophor EL-paclitaxel to the clinic in the mid-1990s, a substantial amount of investigation has gone into subjects such as formulation, dose, schedule, and taxane resistance, allowing physicians greater flexibility in treating patients with MBC. This review will also examine how the shrinking pool of taxane-naive patients, a result of the expansion of taxanes into the neoadjuvant and adjuvant settings, will respond to taxane retreatment for metastatic disease. Taxane treatment seems likely to continue to play an important role in the treatment of MBC.
Identification of the promoter of the myelomonocytic leukocyte integrin CD11b. (1992)

The CD11b (or macrophage-1 antigen; MAC-1) subunit of the leukocyte integrin family forms a noncovalently associated heterodimeric structure with the CD18 (beta) subunit on the surface of human granulocytes and monocyte/macrophages, where it enables these myeloid cells to participate in a variety of adherence-related activities. Expression of the CD11b subunit is restricted to cells of the myelomonocytic lineage and depends upon the stage of differentiation with the most mature myeloid cells expressing the highest levels of CD11b. To study the regulation of CD11b expression, a genomic clone corresponding to the 5' region of the CD11b gene was isolated from a human chromosome 16 library. Primer extension and RNase protection assays identified two major transcriptional start sites, located 90 base pairs and 54 base pairs upstream from the initiation methionine. DNA sequence analysis of 1.7 kilobases of the 5' flanking sequence of the CD11b gene indicated the absence of a "CAAT" or "TATA" box; however, potential binding sites for the transcription activators Sp1, PU.1, ets, and AP-2 are present, as well as retinoic acid response elements. The 1.7-kilobase CD11b promoter sequence displayed functional activity in transient transfection assays in the monocytic cell line THP-1 and the myeloid cell line HL-60. In contrast, this 1.7-kilobase promoter sequence did not display functional activity in the Jurkat T-lymphoid cell line. Detailed characterization of the CD11b promoter sequence should provide insight into the molecular events regulating the tissue-specific and developmental stage-specific expression of the CD11b molecule in myelomonocytic cells.
A Double-Blind Study of Oral Acyclovir for Suppression of Recurrences of Genital Herpes Simplex Virus Infection (1984)

Patients with frequently recurring genital herpes were enrolled in a double-blind placebo-controlled trial comparing 200-mg acyclovir capsules, given five or two times daily, with placebo. Of 47 placebo recipients, 44 (94 per cent) had recurrences during the 120-day treatment period, compared with 13 (29 per cent) of 45 patients treated with acyclovir five times daily and 18 of 51 (35 per cent) treated with acyclovir twice daily (P less than 0.001 for each regimen compared with placebo). The median time to the first clinical recurrence was 18 days in placebo recipients, compared with over 120 days in both acyclovir-treated groups (P less than 0.001 for both groups compared with placebo). The mean monthly recurrence rate during the medication period was 0.86 in placebo recipients, compared with 0.13 in patients treated with acyclovir five times daily and 0.14 in patients treated with acyclovir twice daily (P less than 0.001 for both groups compared with placebo). While receiving therapy, 86 of 96 acyclovir-treated patients had over a 50 per cent reduction in their pretreatment recurrence rate. Breakthrough recurrences in acyclovir recipients were of shorter duration and associated with a lower frequency of viral shedding than recurrences in placebo recipients. After medication was discontinued, the subsequent recurrence rate returned to pretreatment frequencies. Daily oral acyclovir was well tolerated. We conclude that oral acyclovir given for four months markedly reduces but does not completely prevent recurrences of genital herpes and does not influence the long-term natural history of the disease.
Fatty acid‐specific, regiospecific, and stereospecific hydroxylation by cytochrome P450 (CYP152B1) from Sphingomonas paucimobilis: Substrate structure required for α‐hydroxylation (2000)

Fatty acid alpha-hydroxylase from Sphingomonas paucimobilis is an unusual cytochrome P450 enzyme that hydroxylates the alpha-carbon of fatty acids in the presence of H2O2. Herein, we describe our investigation concerning the utilization of various substrates and the optical configuration of the alpha-hydroxyl product using a recombinant form of this enzyme. This enzyme can metabolize saturated fatty acids with carbon chain lengths of more than 10. The Km value for pentadecanoic acid (C15) was the smallest among the saturated fatty acids tested (C10-C18) and that for myristic acid (C14) showed similar enzyme kinetics to those seen for C15. As shorter or longer carbon chain lengths were used, Km values increased. The turnover numbers for fatty acids with carbon chain lengths of more than 11 were of the same order of magnitude (10(3) min(-1)), but the turnover number for undecanoic acid (C11) was less. Dicarboxylic fatty acids and methyl myristate were not metabolized, but monomethyl hexadecanedioate and omega-hydroxypalmitic acid were metabolized, though with lower turnover values. Arachidonic acid was a good substrate, comparable to C14 or C15. The metabolite of arachidonic acid was only alpha-hydroxyarachidonic acid. Alkanes, fatty alcohols, and fatty aldehydes were not utilized as substrates. Analysis of the optical configurations of the alpha-hydroxylated products demonstrated that the products were S-enantiomers (more than 98% enantiomerically pure). These results suggested that this P450 enzyme is strictly responsible for fatty acids and catalyzes highly stereo- and regioselective hydroxylation, where structure of omega-carbon and carboxyl carbon as well as carbon chain length of fatty acids are important for substrate-enzyme interaction.
Externally resonated linear microvibromotor for microassembly (2000)

A new method for on-substrate fine positioning of microscale/mesoscale discrete components is presented, where component positions are finely adjusted using microlinear sliders and fixtures on the substrate. Each microlinear slider is actuated by vibratory impacts exerted by two pairs of microcantilever impacters. These microcantilever impacters are selectively resonated by shaking the entire substrate with a piezoelectric vibrator, requiring no need for built-in driving mechanisms such as electrostatic comb actuators, as reported previously. This selective resonance of the microcantilever impacters via an external vibration energy field provides with a very simple means of controlling forward and backward motion of the microlinear slider, facilitating assembly and disassembly of a microcomponent on a substrate. An analytical model of the device is derived in order to obtain, through the simulated annealing algorithm, an optimal design, which maximizes translation speed of the linear slider at desired external input frequencies. Prototypes of the externally resonated linear microvibromotor are fabricated using the three-layer polysilicon surface micromachining process provided by the Microelectronics Center of North Carolina, Research Triangle Park, NC, multiuser microelectromechanical processes service. These prototypes are tested for forward and backward motion via external vibration applied by an piezoelectric flexure vibrator, as well as the horizontal positioning and release of 500-/spl mu/m-square polysilicon chips against a reference fixture element anchored to the substrate.
Virtual Playgrounds For Worm Behavior Investigation (2005)

Abstract. To detect and defend against Internet worms, researchers have long hoped to have a safe convenient environment to unleash and run real-world worms for close observation of their infection, damage, and propagation. However, major challenges exist in realizing such “worm playgrounds”, including the playgrounds ’ fidelity, confinement, scalability, aswellasconvenience in worm experiments. In this paper, we present a virtualization-based platform to create virtual worm playgrounds, called vGrounds, on top of a physical infrastructure. A vGround is an all-software virtual environment dynamically created for a worm attack. It has realistic end-hosts and network entities, all realized as virtual machines (VMs) and confined in a virtual network (VN). The salient features of vGround include: (1) high fidelity supporting real worm codes exploiting real vulnerable services, (2) strict confinement making the real Internet totally invisible and unreachable from inside a vGround, (3) high resource efficiency achieving sufficiently large scale of worm experiments, and (4) flexible and efficient worm experiment control enabling fast (tens of seconds) and automatic generation, re-installation, and final tear-down of vGrounds. Our experiments with real-world worms (including multi-vector worms and polymorphic worms) have successfully exhibited their probing and propagation patterns, exploitation steps, and malicious payloads, demonstrating the value of vGrounds for worm detection and defense research.
Polymer Brush As a Facile Dielectric Surface Treatment for High-Performance, Stable, Soluble Acene-Based Transistors (2010)

We developed a facile dielectric surface modification using “grafting to” polymer brushes for high-performance and stable TES-ADT FETs. Polymer brushes were grafted onto oxide substrates by spin-coating and thermal annealing. TES-ADT FETs fabricated on top of the polymer brush layer showed excellent device performance−a field-effect mobility of 0.84 cm2/(V s) and an on/off current ratio of 1 × 106−that was superior to that of devices using conventional dielectric surface treatments such as HMDS and ODTS. During solvent annealing of the TES-ADT films, the mobile chains of the polymer brushes appear to profoundly influence the diffusion and crystallization of the TES-ADT molecules, while maximizing the π−π interactions along the in-plane direction. Moreover, the polymer brushes yielded excellent electrical and environmental stability because of the complete surface coverage with minimal pinholes and defects.
<title>Three-dimensional display system based on computer-generated integral photography</title> (2001)

In this paper, we propose a CGIP (Computer-Generated Integral Photography) method and verify its feasibility. In CGIP, the elemental images of imaginary objects are computer-generated instead of using pickup process. Since this system is composed of only one lens array and conventional display devices, it is compact and cost effective. The animated image can also be presented by the time-varying elemental images. As a result, autostereoscopic images with full color and full parallax were observed in real time. Moreover, this method can be applied to a quasi-3D display system. If each camera picks a scene which is a part of total view and elemental images are generated so that each scene has different depth, real objects captured by ordinary cameras can be displayed in quasi-3D. In addition, since it is easy to change the shape or size of elemental images in this scheme, we can observe the effect of several viewing parameters. This helps us to analyze the basic IP system. We perform an experiment with different lens arrays and compare the results. The lateral and depth resolution of the integrated image is limited by some factors such as the image position, object thickness, the lens width, and the pixel size of display panel.
Estimation of Functional Residual Capacity at the Bedside Using Standard Monitoring Equipment: A Modified Nitrogen Washout/Washin Technique Requiring a Small Change of the Inspired Oxygen Fraction (2005)

We developed a modified nitrogen washin/washout technique based on standard monitors using inspiratory and end-tidal gas concentration values for functional residual capacity (FRC) measurements in patients with acute respiratory failure (ARF). For validation we used an oxygen-consuming lung model ventilated with an inspiratory oxygen fraction (Fio(2)) between 0.3 and 1.0. The respiratory quotient of the lung model was varied between 0.7 and 1.0. Measurements were performed changing Fio(2) with fractions of 0.1, 0.2, and 0.3. In 28 patients with ARF, duplicate measurements were performed. In the lung model, an Fio(2) change of 0.1 resulted in a value of 103 +/- 5% of the reference FRC value of the lung model, and the precision was equally good up to an Fio(2) of 1.0 with a value of 103 +/- 7%. In the patients, duplicate measurements showed a bias of -5 mL with a 95% confidence interval [-38; 29 mL ]. A comparison of a change in Fio(2) of 0.1 with 0.3 showed a bias of -9 mL and limits of agreement of [-365; 347 mL]. This study shows good precision of FRC measurements with standard monitors using a change in Fio(2) of only 0.1. Measurements can be performed with equal precision up to an Fio(2) of 1.0.
Molecular characterization of the cAMP-dependent protein kinase bound to microtubule-associated protein 2. (1982)

We have found that a CAMP-dependent protein kinase present in brain microtubule preparations co-purifies with microtubule-associated protein 2 (MAP 2)