gebhart/patrepeval huggingface dataset:
Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways (2017)

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and breast cancer. Various mechanisms mediate the upregulation of EGFR activity, including common mutations and truncations to its extracellular domain, such as in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R and T790M mutations, or the exon 19 truncation. These EGFR aberrations over-activate downstream pro-oncogenic signaling pathways, including the RAS-RAF-MEK-ERK MAPK and AKT-PI3K-mTOR pathways. These pathways then activate many biological outputs that are beneficial to cancer cell proliferation, including their chronic initiation and progression through the cell cycle. Here, we review the molecular mechanisms that regulate EGFR signal transduction, including the EGFR structure and its mutations, ligand binding and EGFR dimerization, as well as the signaling pathways that lead to G1 cell cycle progression. We focus on the induction of <i>CYCLIN D</i> expression, CDK4/6 activation, and the repression of cyclin-dependent kinase inhibitor proteins (CDKi) by EGFR signaling pathways. We also discuss the successes and challenges of EGFR-targeted therapies, and the potential for their use in combination with CDK4/6 inhibitors.
Dynamic performance and control of a static VAr generator using cascade multilevel inverters (1997)

A cascade multilevel inverter is proposed for static VAr compensation/generation applications. The new cascade M-level inverter consists of (M-1)/2 single-phase full bridges in which each bridge has its own separate DC source. This inverter can generate almost sinusoidal waveform voltage with only one time switching per cycle. It can eliminate the need for transformers in multipulse inverters. A prototype static VAr generator (SVG) system using 11-level cascade inverter (21-level line-to-line voltage waveform) has been built. The output voltage waveform is equivalent to that of a 60-pulse inverter. This paper focuses on dynamic performance of the cascade-inverter-based SVG system. Control schemes are proposed to achieve a fast response which is impossible for a conventional static VAr compensator (SVC). Analytical, simulated, and experimental results show the superiority of the proposed SVG system.
Improving the therapeutic window of retinal photocoagulation by spatial and temporal modulation of the laser beam (2011)

Decreasing the pulse duration helps confine damage, shorten treatment time, and minimize pain during retinal photocoagulation. However, the safe therapeutic window (TW), the ratio of threshold powers for thermomechanical rupture of Bruch's membrane and mild coagulation, also decreases with shorter exposures. Two potential approaches toward increasing TW are investigated: (a) decreasing the central irradiance of the laser beam and (b) temporally modulating the pulse. An annular beam with adjustable central irradiance was created by coupling a 532-nm laser into a 200-μm core multimode optical fiber at a 4-7 deg angle to normal incidence. Pulse shapes were optimized using a computational model, and a waveform generator was used to drive a PASCAL photocoagulator (532 nm), producing modulated laser pulses. Acute thresholds for mild coagulation and rupture were measured in Dutch-Belted rabbit in vivo with an annular beam (154-163 μm retinal diameter) and modulated pulse (132 μm, uniform irradiance "flat-top" beam) with 2-50 ms pulse durations. Thresholds with conventional constant-power pulse and a flat-top beam were also determined. Both annular beam and modulated pulse provided a 28% increase in TW at 10-ms duration, affording the same TW as 20-ms pulses with conventional parameters.
A cDNA Encoding S-Adenosyl-L-Methionine:Caffeic Acid 3-O-Methyltransferase from Eucalyptus (1994)

mRNA putatively coding for an O-methyltransferase iiccumulates preferenitially in
Focal adhesion kinase is involved in mechanosensing during fibroblast migration (2001)

Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase localized at focal adhesions and is believed to mediate adhesion-stimulated effects. Although ablation of FAK impairs cell movement, it is not clear whether FAK might be involved in the guidance of cell migration, a role consistent with its putative regulatory function. We have transfected FAK-null fibroblasts with FAK gene under the control of the tetracycline repression system. Cells were cultured on flexible polyacrylamide substrates for the detection of traction forces and the application of mechanical stimulation. Compared with control cells expressing wild-type FAK, FAK-null cells showed a decrease in migration speed and directional persistence. In addition, whereas FAK-expressing cells responded to exerted forces by reorienting their movements and forming prominent focal adhesions, FAK-null cells failed to show such responses. Furthermore, FAK-null cells showed impaired responses to decreases in substrate flexibility, which causes control cells to generate weaker traction forces and migrate away from soft substrates. Cells expressing Y397F FAK, which cannot be phosphorylated at a key tyrosine site, showed similar defects in migration pattern and force-induced reorientation as did FAK-null cells. However, other aspects of F397-FAK cells, including the responses to substrate flexibility and the amplification of focal adhesions upon mechanical stimulation, were similar to that of control cells. Our results suggest that FAK plays an important role in the response of migrating cells to mechanical input. In addition, phosphorylation at Tyr-397 is required for some, but not all, of the functions of FAK in cell migration.
A Numerical Method for Acquisition and Processing of Steady‐State Kinetic Data Contained in an Entire Progression Curve (1973)

A new method is described in which the information available from steady‐state kinetic experiments is thoroughly exploited. The procedure involves varying the concentration of substrate and product, measuring rates along the entire progression curve (general rates), and applying mathematical methods for data processing. Evidence is presented to show that the results are obtained from fewer experiments and that they are more accurate than those obtained by conventional methods. For α‐chymotrypsin‐catalyzed hydrolysis of N ‐acetyl‐ l ‐phenylalanine methyl ester as a substrate the following constants were determined: the dissociation constant of the enzyme‐substrate complex, both rate constants of the acylation step and the forward rate constant of the deacylation step.
Ultrastructural evidence of calcium involvement in experimental autoimmune gray matter disease (2000)

Experimental studies have suggested that increased calcium and inappropriate calcium handling by motoneurons might have a significant role in motoneuron degeneration. To further define the involvement of calcium in motoneuron loss we used the oxalate-pyroantimonate technique for calcium fixation and monitored the ultrastructural distribution of calcium in spinal motoneurons in experimental autoimmune gray matter disease (EAGMD). In cervical and hypoglossal motoneurons from animals with relatively preserved upper extremity and bulbar function, increased calcium precipitates were present in the cytoplasm as well as in mitochondria, endoplasmic reticulum and Golgi complex without significant morphologic alterations. In surviving lumbar motoneurons of animals with hindlimb paralysis, however, there was massive morphological destruction of intracellular organelles but no significant accumulation of calcium precipitates. These findings suggest that altered calcium homeostasis is involved in motoneuron immune-mediated injury with increased calcium precipitates early in the disease process and decreased to absent calcium precipitates later in the pathogenesis of motoneuron injury.
Predicted conversion gain in superconductor-insulator-superconductor quasiparticle mixers (1980)

A computer simulation is constructed to describe the performance of superconductor-insulator-superconductor (SIS) quasiparticle heterodyne receivers in terms of photon-assisted tunneling theory. The results predict that conversion efficiencies greater than unity can be realized at millimeter wave frequencies, with noise temperatures approaching the fundamental quantum limit. The nonlinearity responsible for the mixing is the extremely rapid onset of quasiparticle tunneling current in SIS junctions near the full gap voltage 2Δ/e, and is independent of the Josephson pair currents. Substantial gain is expected under a variety of conditions and for a wide range of source and load impedances.
An afocal electrostatic lens (1971)

The focal properties of a pair of lenses spaced so that the second focal point of one and the first focal point of the other coincide are discussed. It is shown that if the two lenses are identical they form a system with the property of forming an image at a fixed distance from an object and with a magnification that depends only on the overall voltage ratio (as V'/V)-14/). The focal condition which the voltage ratios of each lens must satisfy is shown to be a constant separation of focal points. Calculated focal loci are presented for some equal diameter cylinder lenses.
L-Ascorbic Acid: A Multifunctional Molecule Supporting Plant Growth and Development (2013)

L-Ascorbic acid (vitamin C) is as essential to plants as it is to animals. Ascorbic acid functions as a major redox buffer and as a cofactor for enzymes involved in regulating photosynthesis, hormone biosynthesis, and regenerating other antioxidants. Ascorbic acid regulates cell division and growth and is involved in signal transduction. In contrast to the single pathway responsible for ascorbic acid biosynthesis in animals, plants use multiple pathways to synthesize ascorbic acid, perhaps reflecting the importance of this molecule to plant health. Given the importance of ascorbic acid to human nutrition, several technologies have been developed to increase the ascorbic acid content of plants through the manipulation of biosynthetic or recycling pathways. This paper provides an overview of these approaches as well as the consequences that changes in ascorbic acid content have on plant growth and function. Discussed is the capacity of plants to tolerate changes in ascorbic acid content. The many functions that ascorbic acid serves in plants, however, will require highly targeted approaches to improve their nutritional quality without compromising their health.
Acrylic Ester Polymers (2003)

Abstract The nature of the R group in its formula determines the properties of each acrylic ester and the polymers it forms. Polymers of this class are distinguished by their water‐clear color and stability on aging. Acrylic monomers are extremely versatile building blocks. They readily polymerize or copolymerize with a variety of other monomers. Copolymers with methacrylates, vinyl acetate, styrene, and acrylonitrile are commercially significant. Although the acrylics have a higher cost than many other monomers their unique characteristics and efficiency offset the higher cost. Acrylic ester polymers can be made to hydrolyze to poly(acrylic acid) or an acid salt and the corresponding alcohol. Two principal processes are used for the manufacture of monomeric acrylic esters: the semicatalytic Reppe process and the propylene oxidation process, the latter of which is preferred because of economy and safety. The toxicities of acrylic monomers range from moderate to slight. The vast majority of all commercially prepared acrylic polymers are copolymers of an acrylic ester monomer with one or more different monomers. Copolymerization has led to the development of many different resins for a variety of applications. Acrylic polymers are considered to be nontoxic, and are used primarily in coatings, textiles, adhesives, and paper.
CT Angiography in Suspected Pulmonary Embolism: Impact of Patient Characteristics and Different Venous Lines on Vessel Enhancement and Image Quality (2008)

Patient age and weight showed significant impact on vascular attenuation and image quality in pulmonary CTA with bolus tracking and ATCM, whereas patient sex and different peripheral catheters did not significantly influence image parameters.
Synthese spasmolytisch wirkender Substanzen. XIV. Synthese von Derivaten des Benzilsäureesters mit N‐Methyl‐hydroxy‐piperidin (1962)

Abstract Es wird die Synthese neuer α,α‐Diphenyl‐α‐acyl‐ (bzw. alkoxy)‐essigsäure‐[1‐methylpiperidyl‐(4)]‐ester beschrieben, die sich durch außerordentlich starke spasmolytische Wirksamkeit auszeichnen.
Nucleation of<i>β</i>-Hairpin Structures with Cis Amide Bonds in<i>E</i>-Vinylogous Proline-Containing Peptides (2003)

Synthesis and conformational studies of peptides containing the E-vinylogous prolines 1 (VPro1) and 2 (VPro2), Boc-Ala-Val-VPro1-Xaa-Leu-OMe (3, Xaa = Gly; 4, Xaa = Phe), Boc-Ala-Val-VPro2-Xaa-Leu-OMe (5, Xaa = Gly; 6, Xaa = Phe), Boc-Leu-Ile-Val-VPro1-Xaa-Leu-OMe (7, Xaa = Gly; 8, Xaa = Phe), and Boc-Leu-Ile-Val-VPro2-Xaa-Leu-OMe (9, Xaa = Gly; 10, Xaa = Phe), were carried out. It has been shown that both VPro1 and VPro2 lead to the formation of 12-membered intramolecularly hydrogen bonded structures very similar to type VI beta-turns with a cis Xaa-VPro amide bond in the major conformers in all the peptides 3-10, resulting in the nucleation of beta-hairpin type structures in these molecules in CDCl(3).
The sequence gamma-(312-324) is a fibrin-specific epitope (1991)

Fibrin accelerates the activation of plasminogen catalyzed by tissue- type plasminogen activator much stronger than fibrinogen. Detailed studies showed that (part of) this rate-enhancing effect of fibrin is brought about by two sites in the fibrin molecule: one in A alpha-(148- 160) and one in the gamma-chain stretch 311–379 (also known as FCB-5). During the fibrinogen-to-fibrin conversion, A alpha-(148–160) appears to become accessible, because a monoclonal antibody against synthetic A alpha-(148–160) reacts with fibrin, but not with fibrinogen. Because a similar situation may exist for (at least parts of) FCB-5, we have prepared a monoclonal antibody against a part (ie, gamma-[312–324]) of FCB-5, and found that this is fibrin-specific and does not bind fibrinogen. We conclude that gamma-(312–324) is hidden in fibrinogen and is exposed by the formation of fibrin.
Association between excision repair cross-complementation group 1 polymorphism and clinical outcome of platinum-based chemotherapy in patients with epithelial ovarian cancer (2006)

ERCC1 is a DNA repair gene and has been associated with resistance to DNA damaging agents. In this study we hypothesized that a polymorphism of ERCC1 Asn118Asn (C -> T) might affect the platinum-resistance of epithelial ovarian cancer patients to platinum-taxane chemotherapy administered postoperatively. Using the SNapShot assay, we assessed this polymorphism in ERCC1 in 60 ovarian cancer patients. Platinum-resistance was defined as progression on platinum-based chemotherapy or recurrence within 6 months of completing therapy. Although not significant, platinum-resistance was less frequently observed in patients with the C/T+T/T genotype (P=0.064). Multivariate analysis showed that the C/T+T/T genotypes constituted an independent predictive factor of reduced risk of platinum-resistance in ovarian cancer (odds ratio 0.17, 95% confidence interval 0.04-0.74, P=0.018, Fisher's exact test). No significant correlation was observed between overall survival and the ERCC1 polymorphism. Our results suggest that genotyping of the ERCC1 polymorphism Asn118Asn may be useful for predicting the platinum-resistance of epithelial ovarian cancer patients. However, these findings require prospective confirmation.
Computational design and selections for an engineered, thermostable terpene synthase (2011)

Terpenoids include structurally diverse antibiotics, flavorings, and fragrances. Engineering terpene synthases for control over the synthesis of such compounds represents a long sought goal. We report computational design, selections, and assays of a thermostable mutant of tobacco 5-epi-aristolochene synthase (TEAS) for the catalysis of carbocation cyclization reactions at elevated temperatures. Selection for thermostability included proteolytic digestion followed by capture of intact proteins. Unlike the wild-type enzyme, the mutant TEAS retains enzymatic activity at 65°C. The thermostable terpene synthase variant denatures above 80°C, approximately twice the temperature of the wild-type enzyme.
Butterfly-Net: Optimal Function Representation Based on Convolutional Neural Networks (2018)

Deep networks, especially convolutional neural networks (CNNs), have been successfully applied in various areas of machine learning as well as to challenging problems in other scientific and engineering fields. This paper introduces Butterfly-Net, a low-complexity CNN with structured and sparse cross-channel connections, together with a Butterfly initialization strategy for a family of networks. Theoretical analysis of the approximation power of Butterfly-Net to the Fourier representation of input data shows that the error decays exponentially as the depth increases. Combining Butterfly-Net with a fully connected neural network, a large class of problems are proved to be well approximated with network complexity depending on the effective frequency bandwidth instead of the input dimension. Regular CNN is covered as a special case in our analysis. Numerical experiments validate the analytical results on the approximation of Fourier kernels and energy functionals of Poisson's equations. Moreover, all experiments support that training from Butterfly initialization outperforms training from random initialization. Also, adding the remaining cross-channel connections, although significantly increase the parameter number, does not much improve the post-training accuracy and is more sensitive to data distribution.
Optimizing Functional Accuracy of TMS in Cognitive Studies: A Comparison of Methods (2008)

Transcranial magnetic stimulation (TMS) is a tool for inducing transient disruptions of neural activity noninvasively in conscious human volunteers. In recent years, the investigative domain of TMS has expanded and now encompasses causal structure-function relationships across the whole gamut of cognitive functions and associated cortical brain regions. Consequently, the importance of how to determine the target stimulation site has increased and a number of alternative methods have emerged. Comparison across studies is precluded because different studies necessarily use different tasks, sites, TMS conditions, and have different goals. Here, therefore, we systematically compare four commonly used TMS coil positioning approaches by using them to induce behavioral change in a single cognitive study. Specifically, we investigated the behavioral impact of right parietal TMS during a number comparison task, while basing TMS localization either on (i) individual fMRI-guided TMS neuronavigation, (ii) individual MRI-guided TMS neuronavigation, (iii) group functional Talairach coordinates, or (iv) 10-20 EEG position P4. We quantified the exact behavioral effects induced by TMS using each approach, calculated the standardized experimental effect sizes, and conducted a statistical power analysis in order to calculate the optimal sample size required to reveal statistical significance. Our findings revealed a systematic difference between the four approaches, with the individual fMRI-guided TMS neuronavigation yielding the strongest and the P4 stimulation approach yielding the smallest behavioral effect size. Accordingly, power analyses revealed that although in the fMRI-guided neuronavigation approach five participants were sufficient to reveal a significant behavioral effect, the number of necessary participants increased to n = 9 when employing MRI-guided neuronavigation, to n = 13 in case of TMS based on group Talairach coordinates, and to n = 47 when applying TMS over P4. We discuss these graded effect size differences in light of the revealed interindividual variances in the actual target stimulation site within and between approaches.
Soft Mask Methods for Single-Channel Speaker Separation (2007)

The problem of single-channel speaker separation attempts to extract a speech signal uttered by the speaker of interest from a signal containing a mixture of acoustic signals. Most algorithms that deal with this problem are based on masking, wherein unreliable frequency components from the mixed signal spectrogram are suppressed, and the reliable components are inverted to obtain the speech signal from speaker of interest. Most current techniques estimate this mask in a binary fashion, resulting in a hard mask. In this paper, we present two techniques to separate out the speech signal of the speaker of interest from a mixture of speech signals. One technique estimates all the spectral components of the desired speaker. The second technique estimates a soft mask that weights the frequency subbands of the mixed signal. In both cases, the speech signal of the speaker of interest is reconstructed from the complete spectral descriptions obtained. In their native form, these algorithms are computationally expensive. We also present fast factored approximations to the algorithms. Experiments reveal that the proposed algorithms can result in significant enhancement of individual speakers in mixed recordings, consistently achieving better performance than that obtained with hard binary masks.
A simple protein-based surrogate neutralization assay for SARS-CoV-2 (2020)

Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to the virus within a few weeks of infection, but the duration of this response and how it correlates with clinical outcomes has not been completely characterized. Of particular importance is the identification of immune correlates of infection that would support public health decision-making on treatment approaches, vaccination strategies, and convalescent plasma therapy. While ELISA-based assays to detect and quantitate antibodies to SARS-CoV-2 in patient samples have been developed, the detection of neutralizing antibodies typically requires more demanding cell-based viral assays. Here, we present a safe and efficient protein-based assay for the detection of serum and plasma antibodies that block the interaction of the SARS-CoV-2 spike protein receptor binding domain (RBD) with its receptor, angiotensin-converting enzyme 2 (ACE2). The assay serves as a surrogate neutralization assay and is performed on the same platform and in parallel with an ELISA for the detection of antibodies against the RBD, enabling a direct comparison. The results obtained with our assay correlate with those of 2 viral-based assays, a plaque reduction neutralization test (PRNT) that uses live SARS-CoV-2 virus and a spike pseudotyped viral vector-based assay.
Symmetrical frequency multiplier circuits (1960)

In recent times there has been considerable renewed interest in the use of static magnetic cores to produce power at a multiple of the frequency of a power source. Generally in these circuits, nonlinear magnetic reactors are connected in a symmetrical multiphase fashion, using the cores to produce harmonics and using symmetrical interphase connections to isolate desired groups of harmonics without the use of filters. In previous studies1,2,3 several circuits of this type have been evaluated showing their characteristics when used either as a power supply or as a combined converter and power amplifier.