gebhart/patrepeval huggingface dataset:
Synergistic effects of SHP2 and PI3K pathway inhibitors in GAB2-overexpressing ovarian cancer. (2019)

The scaffold/adaptor growth factor receptor bound 2 (GRB2)-associated binding protein 2 (GAB2) is frequently amplified and/or overexpressed in primary high-grade serous ovarian cancers (HGSOCs). Here we investigate a novel treatment strategy by targeting SHP2 and PI3K signaling in HGSOCs with GAB2 amplification/overexpression (GAB2<sup>High</sup>). The expression of GAB2 was analyzed in primary HGSOCs and ovarian cancer cell lines. <i>In vitro</i> and <i>in vivo</i> assays were performed to demonstrate the effect of SHP2 and PI3K-mediated GAB2<sup>High</sup> HGSOC progression. Analysis of gene expression data reveals that primary GAB2<sup>High</sup> HGSOCs are associated with increased ERBB, RAS, and MAPK activity signatures. Inhibition of SHP2 by an allosteric inhibitor SHP099 selectively inhibits ERK1/2 activity, proliferation, and survival of GAB2<sup>High</sup> ovarian cancer cell lines. Treatment with SHP099 has a synergistic effect with BKM120, a pan-class I PI3K inhibitor, at suppressing proliferation and survival of GAB2<sup>High</sup> ovarian cancer cells <i>in vitro</i> and <i>in vivo</i> by more effectively activating both BIM and BAD and inhibiting c-MYC compared with individual inhibitor. Our findings identify an important role of SHP2 in promoting proliferation and survival of GAB2<sup>High</sup> ovarian cancer cells, and combinatorial SHP2 and PI3K inhibition may be a promising therapeutic approach for such cancer.
Beyond Prostaglandins—Chemistry and Biology of Cyclic Oxygenated Metabolites Formed by Free‐Radical Pathways from Polyunsaturated Fatty Acids (2008)

Polyunsaturated fatty acids (PUFAs) are important constituents in all organisms. They fulfil many functions, ranging from modulating the structure of membranes to acting as precursors of physiologically important molecules, such as the prostaglandins, which for a long time were the most prominent cyclic PUFA metabolites. However, since the beginning of the 1990s a large variety of cyclic metabolites have been discovered that form under autoxidative conditions in vivo to a much larger extent than do prostaglandins. These compounds--isoprostanes, neuroprostanes, phytoprostanes, and isofurans--proved subsequently to be ubiquitous in nature. They display a wide range of biological activities, and isoprostanes have become the currently most reliable indicators of oxidative stress in humans. In a relatively short time, the structural variety, properties, and applications of the autoxidatively formed cyclic PUFA derivatives have been uncovered.
Stochastic Resonance in Bistable Systems (1989)

The relaxation properties of a stochastic bistable system perturbed by a periodic low-frequency forcing term is investigated by means of analog simulation. The so-called stochastic resonance phenomenon is revealed under diverse experimental conditions. Its dependence on the parameters of both the periodic perturbation and the forced system is explained theoretically.
Functional Genomics: Expression Analysis of <i>Escherichia coli</i> Growing on Minimal and Rich Media (1999)

DNA arrays of the entire set of Escherichia coli genes were used to measure the genomic expression patterns of cells growing in late logarithmic phase on minimal glucose medium and on Luria broth containing glucose. Ratios of the transcript levels for all 4,290 E. coli protein-encoding genes (cds) were obtained, and analysis of the expression ratio data indicated that the physiological state of the cells under the two growth conditions could be ascertained. The cells in the rich medium grew faster, and expression of the majority of the translation apparatus genes was significantly elevated under this growth condition, consistent with known patterns of growth rate-dependent regulation and increased rate of protein synthesis in rapidly growing cells. The cells grown on minimal medium showed significantly elevated expression of many genes involved in biosynthesis of building blocks, most notably the amino acid biosynthetic pathways. Nearly half of the known RpoS-dependent genes were expressed at significantly higher levels in minimal medium than in rich medium, and rpoS expression was similarly elevated. The role of RpoS regulation in these logarithmic phase cells was suggested by the functions of the RpoS dependent genes that were induced. The hallmark features of E. coli cells growing on glucose minimal medium appeared to be the formation and excretion of acetate, metabolism of the acetate, and protection of the cells from acid stress. A hypothesis invoking RpoS and UspA (universal stress protein, also significantly elevated in minimal glucose medium) as playing a role in coordinating these various aspects and consequences of glucose and acetate metabolism was generated. This experiment demonstrates that genomic expression assays can be applied in a meaningful way to the study of whole-bacterial-cell physiology for the generation of hypotheses and as a guide for more detailed studies of particular genes of interest.
16.6 A 10b DC-to-20GHz multiple-return-to-zero DAC with >48dB SFDR (2017)

The push towards mm-wave frequencies has increased the demand for UWB DACs with minimal spurious emissions. At mm-wave, intra-DAC dynamic timing and data errors consume a significant portion of the clock period, degrading SFDR. Previously, NRZ and RZ DACs have been reported with output frequencies up to 27GHz [1–4]. However, their outputs are limited to the first two Nyquist zones, requiring high sample rates which exacerbate dynamic errors. Interleaved DACs allow for synthesis above the first Nyquist zone without increasing the sample rate, although inter-DAC amplitude and timing errors introduce additional spurs at the output that can limit SFDR [5,6]. Alternatively, mixing DACs decouple the sample rate and output frequency, however, they do not deglitch the output, limiting SFDR at high frequency [7]. The multiple return-to-zero (MRZ) architecture mitigates the effects of dynamic errors in the data path, allowing for synthesis up to 9.45GHz with 42dB SFDR [8]. Moreover, the use of R-2R networks achieves binary scaling with the same unit cell current, alleviating switch timing mismatches. Although these techniques improve the intrinsic SFDR of the DAC cells, mismatches in the frequency response of routing interconnects dominate the performance at mm-wave. This is especially critical for the output summing node, which requires an identical amplitude and phase response from each cell to the output. Previously reported DACs used simple structures to combine currents at the output, resulting in large phase and amplitude mismatches. Furthermore, the mm-wave operation of the RZ clock exacerbates the effect of timing errors due to both interconnect and transistor mismatches in the RZ path.
Membrane‐bound annexin V isoforms (CaBP33 and CaBP37) and annexin VI in bovine tissues behave like integral membrane proteins (1992)

The distribution of annexin V isoforms (CaBP33 and CaBP37) and of annexin VI in bovine lung, heart, and brain subfractions was investigated with special reference to the fractions of these proteins which are membrane-bound. In addition to EGTA-extractable pools of the above proteins, membranes from lung, heart, and brain contain EGTA-resistant annexins V and VI which can be solubilized with detergents (Triton X-100 or Triton X-114). A strong base like Na2CO3, which is usually effective in extracting membrane proteins, only partially solubilizes the membrane-bound, EGTA-resistant annexins analyzed here. Also, only 50-60% of the Triton X-114-soluble annexins partition in the aqueous phase, the remaining fractions being recovered in the detergent-rich phase. Altogether, these findings suggest that, by an as yet unknown mechanism, following Ca(2+)-dependent association of annexin V isoforms and annexin VI with membranes, substantial fractions of these proteins remain bound to membranes in a Ca(2+)-independent way and behave like integral membrane proteins. These results further support the possibility that the above annexins might play a role in membrane trafficking and/or in the regulation of the structural organization of membranes.
Interventions for treating oral leukoplakia (2006)

To date there is no evidence of effective treatment in preventing malignant transformation of leukoplakia. Treatments may be effective in the resolution of lesion, however relapses and adverse effects are common.
The serine acetyltransferase from <i>Escherichia coli</i> (1990)

An expression vector has been constructed which increases the expression of serine acetyltransferase (SAT) from E. coli to 17% of the soluble cell protein. A novel purification procedure, using dye-affinity chromatography, allows purification of SAT to homogeneity. The enzyme has been crystallised from polyethylene glycol, in the presence of L-cysteine (an inhibitor of SAT). The crystals which diffract to beyond 3.0 A resolution are of the tetragonal spacegroup P4(1)2(1)2 (or P4(3)2(1)2) with cell dimensions a = b = 123 A, c = 79 A. Since ultracentrifugation and gel-filtration experiment indicate that purified SAT is a tetramer, there appears to be one-half tetramer in the asymmetric unit (Vm = 2.55 A3/Da).
Generation of cell-to-cell signals in quorum sensing: acyl homoserine lactone synthase activity of a purified Vibrio fischeri LuxI protein. (1996)

Many bacteria use acyl homoserine lactone signals to monitor cell density in a type of gene regulation termed quorum sensing and response. Synthesis of these signals is directed by homologs of the luxi gene of Vibrio fischeri. This communication resolves two critical issues concerning the synthesis of the V. fischeri signal. (i) The luxI product is directly involved in signal synthesis-the protein is an acyl homoserine lactone synthase; and (ii) the substrates for acyl homoserine lactone synthesis are not amino acids from biosynthetic pathways or fatty acid degradation products, but rather they are S-adenosylmethionine (SAM) and an acylated acyl carrier protein (ACP) from the fatty acid biosynthesis pathway. We purified a maltose binding protein-LuxI fusion polypeptide and showed that, when provided with the appropriate substrates, it catalyzes the synthesis of an acyl homoserine lactone. In V. fischeri, luxi directs the synthesis of N-(3-oxohexanoyl) homoserine lactone and hexanoyl homoserine lactone. The purified maltose binding protein-LuxI fusion protein catalyzes the synthesis of hexanoyl homoserine lactone from hexanoyl-ACP and SAM. There is a high level of specificity for hexanoyl-ACP over ACPs with differing acyl group lengths, and hexanoyl homoserine lactone was not synthesized when SAM was replaced with other amino acids, such as methionine, S-adenosylhomocysteine, homoserine, or homoserine lactone, or when hexanoyl-SAM was provided as the substrate. This provides direct evidence that the LuxI protein is an auto-inducer synthase that catalyzes the formation of an amide bond between SAM and a fatty acyl-ACP and then catalyzes the formation of the acyl homoserine lactone from the acyl-SAM intermediate.
Ratio of Plasma Alpha Amino- <i>n</i> -Butyric Acid to Leucine as an Empirical Marker of Alcoholism: Diagnostic Value (1977)

The ratio of plasma alpha amino-n-butyric acid to leucine was raised in patients with both alcohol-related and nonalchol-related liver disease. This ratio appears to act as a relatively nonsensitive index of hepatocellular dysfunction rather than an index of alcoholism.
Electrocardiogram synthesis using a Gaussian combination model (GCM) (2007)

In this paper modifications to an algorithm for electrocardiogram (ECG) synthesis based on a combination of Gaussians to fit real ECG data have been proposed. A method is proposed for fitting algorithm assuming that constituent Gaussian functions in GCM model are independent. Desired period(s) of ECG were selected and the number of Gaussians in the morphologic model was determined. For ECG synthesis, a Gaussian was fitted around each of the extrema and minimized local error that is defined as local difference of real ECG and our model. The range of Gaussian fitting (place to put independent Gaussian) was determined using two methods: zero crossing method and minimum bank method. Results were presented based on the efficiency of determining the Gaussian parameters in terms of time for fitting and accuracy of model.
Platelet transfusions are associated with the development of anti-major histocompatibility complex class I antibodies in patients with left ventricular assist support. (1998)

These results indicate that platelet transfusion during LVAD implantation is a risk factor associated with development of HLA class I IgG antibodies. Use of leukocyte filters during platelet transfusion may decrease the risk of development of anti-HLA antibodies.
Activation of Complement Component C5 (2008)

Although the initiating complex of lectin pathway (called M1 in this study) generates C3/C5 convertases similar to those assembled by the initiating complex (C1) of the classical pathway, activation of complement component C5 via the lectin pathway has not been examined. In the present study kinetic analysis of lectin pathway C3/C5 convertases assembled on two surfaces (zymosan and sheep erythrocytes coated with mannan (E(Man))) revealed that the convertases (ZymM1,C4b,C2a and E(Man)M1,C4b,C2a) exhibited a similar but weak affinity for the substrate, C5 indicated by a high K(m) (2.73-6.88 microm). Very high affinity C5 convertases were generated when the low affinity C3/C5 convertases were allowed to deposit C3b by cleaving native C3. These C3b-containing convertases exhibited K(m) (0.0086-0.0075 microm) well below the normal concentration of C5 in blood (0.37 microm). Although kinetic parameters, K(m) and k(cat), of the lectin pathway C3/C5 convertases were similar to those reported for classical pathway C3/C5 convertases, studies on the ability of C4b to bind C2 indicated that every C4b deposited on zymosan or E(Man) was capable of forming a convertase. These findings differ from those reported for the classical pathway C3/C5 convertase, where only one of four C4b molecules deposited formed a convertase. The potential for four times more amplification via the lectin pathway than the classical pathway in the generation of C3/C5 convertases and production of pro-inflammatory products, such as C3a, C4a, and C5a, implies that activation of complement via the lectin pathway might be a more prominent contributor to the pathology of inflammatory reactions.
Tetrathiomolybdate promotes tumor necrosis and prevents distant metastases by suppressing angiogenesis in head and neck cancer (2007)

Angiogenesis is well recognized as an essential process that influences not only the growth of head and neck squamous cell carcinoma (HNSCC) but also promotes its invasive and metastatic behavior. The critical role of copper in multiple facets of angiogenesis makes it an important therapeutic target. Tetrathiomolybdate is a potent copper chelator, which has shown remarkable ability to suppress angiogenesis. Although this may involve multiple mechanisms, the effects on vascular endothelial growth factor (VEGF) are pivotal. In previous work, tetrathiomolybdate suppressed production of several proangiogenic cytokines by HNSCC cell lines. Given these results, we hypothesized that tetrathiomolybdate would impair tumor growth and metastasis by HNSCC. To test this concept, we evaluated the effects of long-term tetrathiomolybdate treatment on the growth and metastatic progression of HNSCC using a xenograft animal model. The results showed that tetrathiomolybdate treatment is able to maintain effective inhibition of angiogenesis. There was a significant reduction in the tumor size and vascularity with evident gross necrosis in the tetrathiomolybdate-treated animals. These effects were highly correlated with suppression of human VEGF expressed in the developing tumors as well as the mouse VEGF levels detected in the plasma. Moreover, tetrathiomolybdate treatment drastically suppressed the development of lung metastases. Taken together, these results show that tetrathiomolybdate can act long-term as a suppressor of vascularity and inhibit the growth of metastasis in this model of HNSCC.
Enterprise-wide management: a paradigm for constructing organizational decision support systems (2002)

Presents the enterprise management problem solving paradigm (EMP), a general approach for building organizational decision support systems capable of solving complex enterprise management problems. The authors describe the formalism upon which EMP is based and the fundamental concepts involved with EMP-based problem solutions. In particular, they discuss the cornerstone of EMP systems, the probot ('process robot'), and introduce the Campbell-Whitehair conjecture, which suggests constraints that can be used to effectively reduce the cost of problem solving in many enterprise management domains. They also discuss several research projects that validate EMP, some results from initial efforts to prototype comprehensive enterprise management systems, and some of the more significant issues encountered during these efforts.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
A software defined approach to unified IPv6 transition (2013)

The IPv6 transition has been an ongoing process throughout the world due to the exhaustion of the IPv4 address space. However, this transition leads to costly end-to-end network upgrades and poses new challenges of managing a large number of devices with a variety of transitioning protocols. Recognizing these difficulties, we propose an software defined approach to unifying the deployment of IPv6 in a cost-effective, flexible manner. Our deployment and experiments demonstrate significant benefits of this approach, including low complexity, low cost and high flexibility of adopting different existing transition mechanisms.
Perturbation analysis of nearly uniform coupled waveguide arrays (1986)

The use of perturbation theory for determining the eigenvalues and eigenvectors (characteristic mode shapes) of nearly uniform coupled waveguide arrays is examined. The method has relevance to large waveguide arrays, for example, phase-locked array lasers, where the exact solution may be difficult to obtain. The results are compared to the exact solution of the eigenvalue problem, and, where possible, simplified results are derived for the effects of particular perturbations.
Nano-Confinement Induced Chain Alignment in Ordered P3HT Nanostructures Defined by Nanoimprint Lithography (2009)

Control of polymer morphology and chain orientation is of great importance in organic solar cells and field effect transistors (OFETs). Here we report the use of nanoimprint lithography to fabricate large-area, high-density, and ordered nanostructures in conjugated polymer poly(3-hexylthiophene) or P3HT, and also to simultaneously control 3D chain alignment within these P3HT nanostructures. Out-of-plane and in-plane grazing incident X-ray diffraction were used to determine the chain orientation in the imprinted P3HT nanostructures, which shows a strong dependence on their geometry (gratings or pillars). Vertical chain alignment was observed in both nanogratings and nanopillars, indicating strong potential to improve charge transport and optical properties for solar cells in comparison to bulk heterojunction structure. For P3HT nanogratings, pi-pi stacking along the grating direction with an angular distribution of +/-20 degrees was found, which is favorable for OFETs. We propose the chain alignment is induced by the nanoconfinement during nanoimprinting via pi-pi interaction and hydrophobic interaction between polymer chain and mold surfaces.
Local motion estimation and resolution enhancement of video sequences (2002)

This paper describes a method for producing a sequence of higher resolution images from a sequence of low-resolution images containing sub-pixel shifts. This is possible in cases where aliasing is caused by the digitization process, and images of the low-resolution video sequence contain slightly different, but unique, information. The motion estimation is obtained by the respective group delays of local adaptive filters for optimal linear prediction. The main idea of the proposed iterative super resolution algorithm is that each high-resolution frame in the output sequence is generated from the previous high-resolution frame and a correction image. The correction image is the back projected filtered difference between the observed low-resolution image and the image obtained from the previous high-resolution frame using a simulation of the imaging system.
Towards 10  Gb/s orthogonal frequency division multiplexing-based visible light communication using a GaN violet micro-LED (2017)

Visible light communication (VLC) is a promising solution to the increasing demands for wireless connectivity. Gallium nitride micro-sized light emitting diodes (micro-LEDs) are strong candidates for VLC due to their high bandwidths. Segmented violet micro-LEDs are reported in this work with electrical-to-optical bandwidths up to 655 MHz. An orthogonal frequency division multiplexing-based VLC system with adaptive bit and energy loading is demonstrated, and a data transmission rate of 11.95 Gb/s is achieved with a violet micro-LED, when the nonlinear distortion of the micro-LED is the dominant noise source of the VLC system. A record 7.91 Gb/s data transmission rate is reported below the forward error correction threshold using a single pixel of the segmented array when all the noise sources of the VLC system are present.
Usability Challenges of PKI (2008)

Security mechanisms can only be effective if they are usable as well. Above all, this statement applies to systems based on public key infrastructures (PKI) due to their high complexity. In practice PKI has been found to be a source for user errors, which could easily lead to security breaches. On the other hand usability problems hinder the usage and deployment of PKI-enabled applications and services. The dissertation at hand describes challenges specific for PKI technology with regard to usability and presents possible solutions. A general multi-layer model of methods to promote usable security is introduced as well as a generic tool for the analysis of PKI-enabled applications of any kind. The thesis subsequently exemplifies several applications of these concepts: Beside technical protection mechanisms, user sensitization and training are important pillars of IT security since a lot of security problems can be traced back to human error or negligence. We develop a new approach for security awareness campaigns aiming at long-term and sustainable changes in behaviour by means of direct user involvement. Delegating security-critical tasks is one possibility to face usability issues. Here we focus on PKI outsourcing, i.e. the operation of a trustcenter by a service provider. In this setting, a secure certificate enrolment process is of particular importance. We point out a weakness of the standard protocol and show how to repair it with the help of a four-eyes principle realized by distributed digital signatures. Our protocol requires a distributed key generation by two parties. For this purpose we present a new, efficient and provably secure algorithm for RSA. Most email programs already support encryption and digital signatures, but these features are hardly used in practice. An important reason for this is the unfavourable cost-benefit ratio from the user's point of view. We show how to improve this ratio with the help of opportunistic security. This allows using public key cryptography without certificates and the costs associated with them. PKI-based authentication schemes suffer from the restriction that, due to security reasons, cryptographic keys cannot be temporarily delegated to a proxy for instance during holidays. We present a uniform and seamless solution for the World Wide Web that supports all common authentication mechanisms.