gebhart/patrepeval huggingface dataset:
Abstract LB-418: Targeting the PI3K/mTOR pathway in genetically engineered mouse models of prostate cancer (2011)

Abstract The PTEN and p53 tumor suppressors are among the most commonly inactivated or mutated genes in human cancer, including prostate cancer. Loss of PTEN is associated with increased pathologic Gleason score and risk of clinical recurrence, and 20-60% of human metastatic prostate cancers have loss of heterozygosity at the PTEN locus, resulting in hyperactivation of the PI3K/mTOR pathway. Mice with germline heterozygosity for PTEN have been shown to develop prostate intraepithelial neoplasia (PIN) at a high rate (&amp;gt;60%) and mice with prostate specific homozygous deletion of PTEN develop invasive prostate cancer, albeit with prolonged latency of approx. 6 months. Combined inactivation of PTEN and p53 in mouse prostate elicits invasive cancer by 9 weeks of age and invariable lethality by 7 months of age. There are several PI3K pathway-directed therapies currently in Phase I clinical trials, but the underlying tumor genetic signature of patients most likely to respond to these therapies is largely unknown. To understand the significance of targeting the PI3K/mTOR pathway in advanced prostate cancer driven by PTEN +/− p53 loss, we evaluated the impact of GSK458 (a dual PI3K/mTOR inhibitor) in prostate-specific PTEN/p53 double knockout mice and prostate-specific PTEN-knockout mice. The mice were imaged by synchronized 18FDG-PET and T2-weighted MRI, respectively, for baseline tumor metabolic and volumetric assessment prior to drug administration. GSK458 was administered at 3 mg/kg by daily oral gavage for 3 weeks with serial 18FDG-PET and T2-weighted MRI imaging at 2 days, 1 week, 2 weeks and 3 weeks after initiation of treatment, followed by sacrifice, prostate harvest and standard hisopathologic and immunohistochemical staining. GSK458 treatment of PTEN/p53-deficient and PTEN-deficient mice results in target inhibition, based on pharmacodynamic assessment by 18FDG-PET uptake. MRI and histopathologic analysis demonstrate that there is a significant reduction, but not complete regression of tumor burden in both intraepithelial and poorly differentiated atypical components within stroma and partial stromal collapse following 3 weeks of GSK458 treatment. These data highlight the feasibility of monitoring dual pharmacodynamics/antitumor effects of PI3K-directed therapies using 18FDG-PET/MRI imaging and underscore the utility of genetically engineered mouse models to predict response to targeted therapies in genetically stratified human clinical trials. The evaluation of PI3K-isoform specific inhibitors and the design of rational combinations to overcome de novo and acquired resistance mechanisms to PI3K-directed therapies are currently being explored in multiple genetically engineered mouse model systems. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-418. doi:10.1158/1538-7445.AM2011-LB-418
A carrier and timing recovery technique for QAM transmission on digital subscriber loops (2002)

The asymmetric digital subscriber line (ADSL) service attempts to provide 1.6 Mb/s data transmission over a single twisted-pair copper loop for distances up to 18 kft. A simple timing and carrier recovery scheme for a quadrature amplitude modulation (QAM) approach is proposed. The algorithm uses the receiver decisions to eliminate the effects of intersymbol interference (ISI) as well as to provide estimates for samples of the pulse response at the demodulator output. These estimates are then used to generate a sampling phase error signal that can be used in a single phase locked loop configuration to correct carrier frequency, as well as timing offsets in the QAM based system. The algorithm exploits the characteristics of both the system as well as the environment, and is simple enough to allow integration with all other receiver blocks on a single integrated circuit. Preliminary results for an ADSL system with blind equalization starting from an unequalized state are presented. The new scheme is shown to be effective at acquiring and tracking frequency offsets as high as 112 ppm, without significantly degrading system performance.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effects of cerebral ischemia in mice deficient in Persephin (2002)

Persephin (Pspn), a recently cloned member of the transforming growth factor-beta superfamily (TGF-beta) and glial cell line-derived neurotrophic factor (GDNF) subfamily, is distributed throughout the nervous system at extremely low levels and is thought to function as a survival factor for midbrain dopaminergic and spinal motor neurons in vivo. Here, we report that mice lacking Pspn by homologous recombination show normal development and behavior, but are hypersensitive to cerebral ischemia. A 300% increase in infarction volume was observed after middle cerebral artery occlusion. We find that glutamate-induced Ca(2+) influx, thought to be a major component of ischemic neuronal cell death, can be regulated directly by the Persephin protein (PSP) and that PSP can reduce hypoxia/reperfusion cell death in vitro. Neuronal cell death can be prevented or markedly attenuated by administration of recombinant human PSP in vivo before ischemia in both mouse and rat models. Taken together, these data indicate that PSP is a potent modulator of excitotoxicity in the central nervous system with pronounced neuroprotective activity. Our findings support the view that PSP signaling can exert an important control function in the context of stroke and glutamate-mediated neurotoxicity, and also suggest that future therapeutic approaches may involve this novel trophic protein.
Characterization of the performance of capacitive switches activated by mechanical shock (2007)

This paper presents experimental and theoretical investigation of a new concept of switches (triggers) that are actuated at or beyond a specific level of mechanical shock or acceleration. The principle of operation of the switches is based on dynamic pull-in instability induced by the combined interaction between electrostatic and mechanical shock forces. These switches can be tuned to be activated at various shock and acceleration thresholds by adjusting the DC voltage bias. Two commercial off-the-shelf capacitive accelerometers operating in air are tested under mechanical shock and electrostatic loading. A single-degree-of-freedom model accounting for squeeze-film damping, electrostatic forces, and mechanical shock is utilized for the theoretical investigation. Good agreement is found between simulation results and experimental data. Our results indicate that designing these new switches to respond quasi-statically to mechanical shock makes them robust against variations in shock shape and duration. More importantly, quasi-static operation makes the switches insensitive to variations in damping conditions. This can be promising to lower the cost of packaging for these switches since they can operate in atmospheric pressure with no hermetic sealing or costly package required.
BR1: A New Ultrasonographic Contrast Agent Based on Sulfur Hexafluoride-Filled Microbubbles (1995)

Considering its high echogenicity, outstanding stability, and resistance to pressure changes, BR1 is a very promising ultrasound contrast agent.
On regret of parametric mismatch in minimum mean square error estimation (2010)

This paper studies the effect of parametric mis-match in minimum mean square error (MMSE) estimation. In particular, we consider the problem of estimating the input signal from the output of an additive white Gaussian channel whose gain is fixed, but unknown. The input distribution is known, and the estimation process consists of two algorithms. First, a channel estimator blindly estimates the channel gain using past observations. Second, a mismatched MMSE estimator, optimized for the estimated channel gain, estimates the input signal. We analyze the regret, i.e., the additional mean square error, that is raised in this process. We derive upper-bounds on both absolute and relative regrets. Bounds are expressed in terms of the Fisher information. We also study regret for unbiased, efficient channel estimators, and derive a simple trade-off between Fisher information and relative regret. This trade-off shows that the product of a certain function of relative regret and Fisher information equals the signal-to-noise ratio, independent of the input distribution. The trade-off relation implies that higher Fisher information results to smaller expected relative regret.
All-fiber CARS microscopy of live cells (2009)

Using an all-fiber laser system consisting of a femtosecond Er/Yb fiber oscillator as the pump and an ultra-highly nonlinear fiber for Stokes generation, we demonstrate multimodal (TPF+SHG+CARS) non-linear optical microscopy of both tissue samples and live cells. Multimodal imaging was successfully performed with pixel dwell times as short as 4 micros at low laser powers (< 40 mW total).
Binding of insulin to isolated nuclei. (1976)

Specific binding sites for 125I-labeled insulin were detected in purified nuclei isolated from rat liver. Binding was rapid, reversible and directly proportional to the number of nuclei employed. Unlabeled native insulin, at concentrations as low as 1ng/ml, significantly inhibited the binding of labeled hormone, whereas unlabeled proinsulin and desoctapeptide insulin were less potent. In contrast, glucagon, thyrotropin, growth hormone (somatotropin), and prolactin were without effect. Under identical incubation conditions, 125I-labeled glucagon bound to liver plasma membranes 5- to 10-fold more strongly than did insulin; in contrast glucoagon did not bind to liver nuclei. These studies demonstrate the presence of specific binding sites for insulin in purified nuclei isolated from rat liver. In addition, they suggest that the nucleus may be an intracellular site of insulin action.
In Vitro Complement-Dependent Cytotoxicity and Antibody-Dependent Cellular Cytotoxicity by the Anti-TNF Agents Adalimumab, Etanercept, Infliximab, and Certolizumab Pegol (CDP870) (2005)

Purpose: To determine the ability of the anti-TNF agents adalimumab, etanercept, infliximab, and certolizumab pegol to kill cells expressing membrane TNF by complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Methods: NS0 cells transfected with human TNF (TNF 6.5 cell line) were used for this study. These cells express high levels of membrane TNF on their cell surface. Directly fluoresceinated reagents were used to determine the level of binding of the anti-TNF agents compared with negative control reagents on the TNF 6.5 cell line by flow cytometry. CDC of the TNF 6.5 cell line by the different reagents was determined by measuring lactate dehydrogenase release from the cells and by measuring propidium iodide (PI) staining using flow cytometry. ADCC was performed on the TNF 6.5 cells using monocyte-depleted peripheral blood mononuclear cells as the effector cells. Cell killing was also quantified using PI staining measured by flow cytometry. Results: All four anti-TNF agents bound to the membrane TNF on the TNF 6.5 cells, although etanercept bound to a lesser degree than the other reagents. However, CDC and ADCC of TNF 6.5 cells were mediated only by adalimumab, etanercept, and infliximab, which all have an active human IgG1 Fc. Certolizumab pegol did not kill cells by either method because it is a PEGylated Fab' fragment that does not have an Fc region. Conclusions: It has been reported that etanercept does not mediate CDC or ADCC. However, in this model system, etanercept was clearly capable of killing TNF 6.5 cells by both methods, similar to infliximab and adalimumab. Owing to its unique structure, certolizumab pegol is the only anti-TNF agent that did not mediate in vitro killing by CDC or ADCC of cells expressing TNF on their membrane.
Meteoritic Cα‐Methylated α‐Amino Acids and the Homochirality of Life: Searching for a Link (2004)

Sternschnuppen: Peptide aus chiralen, Cα-methylierten α-Aminosäuren (siehe Schema), die in Meteoriten vorwiegend als L-Enantiomere nachgewiesen wurden, reagieren mit racemischen proteinogenen Aminosäuren diastereoselektiv. Daher könnte sich die Ursuppe proteinogener Aminosäuren zu einem chiral nicht ausbalancierten System entwickelt haben und so Ursprung der Homochiralität des Lebens geworden sein. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2004/z460908_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
A Versatile Family 3 Glycoside Hydrolase from Bifidobacterium adolescentis Hydrolyzes β-Glucosides of the Fusarium Mycotoxins Deoxynivalenol, Nivalenol, and HT-2 Toxin in Cereal Matrices (2015)

Glycosylation plays a central role in plant defense against xenobiotics, including mycotoxins. Glucoconjugates of Fusarium toxins, such as deoxynivalenol-3-O-β-d-glucoside (DON-3G), often cooccur with their parental toxins in cereal-based food and feed. To date, only limited information exists on the occurrence of glucosylated mycotoxins and their toxicological relevance. Due to a lack of analytical standards and the requirement of high-end analytical instrumentation for their direct determination, hydrolytic cleavage of β-glucosides followed by analysis of the released parental toxins has been proposed as an indirect determination approach. This study compares the abilities of several fungal and recombinant bacterial β-glucosidases to hydrolyze the model analyte DON-3G. Furthermore, substrate specificities of two fungal and two bacterial (Lactobacillus brevis and Bifidobacterium adolescentis) glycoside hydrolase family 3 β-glucosidases were evaluated on a broader range of substrates. The purified recombinant enzyme from B. adolescentis (BaBgl) displayed high flexibility in substrate specificity and exerted the highest hydrolytic activity toward 3-O-β-d-glucosides of the trichothecenes deoxynivalenol (DON), nivalenol, and HT-2 toxin. A Km of 5.4 mM and a Vmax of 16 μmol min(-1) mg(-1) were determined with DON-3G. Due to low product inhibition (DON and glucose) and sufficient activity in several extracts of cereal matrices, this enzyme has the potential to be used for indirect analyses of trichothecene-β-glucosides in cereal samples.
Addressing Reliability Needs of Industrial Applications in 5G NR with Network Coding (2020)

Industrial applications introduce new and complex requirements in terms of reliability and latency for wireless communication systems. In particular, 3GPP has recently identified the need for communications being ultra reliable as well as robust against consecutive packet errors. These requirements call for new approaches that span multiple layers to encompass the latency-reliability trade-offs compared to classical error correction schemes like (Hybrid) ARQ. For this purpose, techniques like puncturing, power boosting, and data duplication have been introduced in 5G NR to enable transmission preemption and overriding, and data redundancy. To alleviate their radio inefficiency cost, this paper presents network coding schemes that proactively correct packet errors caused by simultaneous or consecutive leg transmission failures. In particular, we demonstrate that the proposed schemes are able to increase the reliability of single and consecutive packet transmissions while reducing the associated traffic increase as compared to data duplication.
Effect of hot isostatic pressing on the microstructure and fracture toughness of laser additive-manufactured MoSiBTiC multiphase alloy (2020)

MoSiB-based alloys are extremely promising ultrahigh–temperature materials, owing to their high melting points, good thermal stability, and excellent elevated-temperature mechanical properties. However, their fabrication is limited to conventional manufacturing techniques. In this work, a MoSiBTiC multiphase alloy, mainly consisting of Mo solid solution (Moss), Mo5SiB2 (T2), and TiC phases, was fabricated by laser powder bed fusion (L-PBF) using ball-milled alloy powders; subsequently, the effect of hot isostatic pressing (HIP) on its microstructure and fracture toughness was investigated. Due to the non-equilibrium metallurgical characteristics of L-PBF, the as-built alloy included uniform and fine-grained structures, as well as internal microcracks. The length of microcracks was effectively reduced with the assistance of the TiC bridging effect during HIP. As revealed by a high-resolution transmission electron microscope, the TiC was uniformly dispersed and was in close contact with the Moss or T2 phase. Consequently, the MoSiBTiC multiphase alloy exhibited a high fracture toughness of 9.0 MPa(m)1/2 after HIP at 1973 K. This work could be an important step towards the fabrication of high-performance refractory components with advanced properties in ultrahigh–temperature use.
Differences in Herbicidal Activity, Phytotoxic Symptom and Auxin Activity of Quinclorac among Plant Species Compared with 2,4-D. (1991)

Greenhouse experiments were conducted with 35 plant species to evaluate the selectivity and symptoms caused by quinclorac (BAS 514 H; 3, 7-dichloro-8-quinolinecarboxylic acid) as compared with 2, 4-D (2, 4-dichlorophenoxyacetic acid). The grass species tested fell into groups either susceptible or tolerant to quinclorac based on their sensitivity and morphological responses. The susceptible group included Echinochloa spp., Setaria spp., Digitaria sanguinalis, Panicum dichotomiflorum and Zea mays, and the tolerant group included Oryza sativa, Triticum aestivum, Sorghum bicolor, Avena sativa, Elusine indica, Dactylis glomerata, Arthraxon hispidus and Alopecurus aeqularis. Quinclorac-susceptible grasses showed different symptoms from those caused by 2, 4-D: chlorosis, necosis of newly emerged leaf, and finally stunting and desiccation of the entire plant. Most broad-leaves were susceptible to quinclorac and showed auxin-like symptoms, except for Brassica napus, Raphanus sativa, Capsicum annuum and Commelina communis, which were tolerant. The auxin activity of quinclorac was evaluated by bioassays. In mesocotyl elongation response of barnyardgrass and sorghum, 2, 4-D showed the auxin activity on both species, but quinclorac showed it on sorghum alone. In petiole curvature response of radish and velvetleaf, 2, 4-D showed the auxin activity on both species, quinclorac showed it only on velvetleaf. It is suggested that the mode of action of quinclorac on susceptible grasses is not related to auxin activity.
[Validity of an ELISA test for CD4+ T lymphocyte count and validity of total lymphocyte count in the assessment of immunodeficiency status in HIV infection]. (1994)

A newly available commercial ELISA (TRAx CD4, T Cell Diagnostics USA) for enumerating CD4+ T lymphocytes has been evaluated with blood samples of 105 HIV seropositive and 6 seronegative subjects. Results from the flow cytometric analysis were used as reference. The sensitivity and specificity of the ELISA to identify HIV seropositive subjects having less than 200 CD4+ T lymphocytes/microliters were assessed and studied using the ROC curve. The reproducibility of the ELISA test was analyzed on 40 samples. The results of the ELISA correlated well with these of the flow cytometric analysis (r = 0.79, p < 0.001). However, the ELISA test tends to overestimate the true CD4 count in HIV seropositives. This overestimation could not be explained by the aspecific contribution of monocytic CD4. The threshold for identifying HIV seropositive subjects with less than 200 CD4+ T lymphocytes with a maximum sensitivity and specificity was determined with ROC curve and equalled 400 cell equivalents with the ELISA (sensitivity and specificity were equal to 80%) and 1,450 lymphocytes/microliters with the total absolute lymphocyte count (sensitivity and specificity were equal to 75%). Using this curve, a threshold of 300 cell equivalents for the ELISA test and of 1,100 lymphocytes/microliters for the absolute lymphocyte count was shown to maximize the specificity (> 95%) without a significant loss of sensitivity.
Grundlegende Analyse der Schreib- und Leseoperationen in passiven Crossbar-Strukturen mit resistiv schaltenden Materialien (2015)

By reaching atomic dimensions, the end of Moore’s Law is near, not only due to economic reasons, but also physical reasons. A next generation technology that could continue the success of CMOS in microelectronics has currently not been identified for integrated logic circuits or for memory. There are however promising concepts of devices that could allow for further scaling in a hybrid combination with CMOS circuits. For example, for future non-volatile memories, devices are under research that are based on switching materials and show two stable resistive states. Without selection transistors, the size of a memory cell is only dependent on the electrode dimensions and can be theoretically realized in the smallest possible area of 4F². Such layouts, where the intersection of a word and bit line simultane-ously forms the connecting electrodes of the memory cell, are called passive crossbar arrays. As long as the memory elements show a sufficient amount of directivity, writing to and reading from such crossbar arrays with active CMOS circuits can be realized.This dissertation addresses the actual and challenging question; which write or read schemes are the most beneficial and what design space arises due to the memory element properties given their fundamental limits. This applies even more for state-of-the-art memory elements as directivity is not easily accomplished. Without such directivity currents going through non-selected cells, aggravate reading and writing renders these operations impossible. A simplified equivalent circuit diagram was developed for which the nodes and mesh equations for different read/write-circuits could be solved in closed-form. This mathematic model is used to analyze the impact of parasitic elements in the array and is supported by a simulative approach. On the basis of these two approaches, different concepts for read and write operations are investigated and benchmarked in reference to performance, susceptibil-ity to parasitic elements, and power consumption.By introducing active CMOS feedback circuits, it can be shown that read and write access to passive crossbar arrays is possible with sufficient margins. The results of this fundamental analysis could deliver useful information for the further technological optimization of hysteretic resistive switches. It also provides a basis for benchmarking between scaled CMOS and hybrid crossbar arrays.
ON-CHIP DEVICE FOR ISOTHERMAL, CHEMICAL CYCLING POLYMERASE CHAIN REACTION (2008)

We demonstrate a novel chemical cycling polymerase chain reaction (ccPCR) technique for DNA amplification in a fully working device where temperature is held constant in space and time. We demonstrate successful ccPCR amplification while simultaneously focusing products via isotachophoresis (ITP) for identification of the environmental bacteria E. Coli. We electrophoretically drive the DNA sample with ITP through a series of high denaturant concentration zones. The denaturant is neutral so the DNA experiences alternatively low and high concentrations. This effectively replaces the thermal cycling of classical PCR (Figure 1). We performed ccPCR with end-point detection and real-time fluorescence monitoring.