gebhart/patrepeval huggingface dataset:
A novel therapeutic opportunity for the most aggressive sub‐type of pancreatic cancer: Targeting keratin 17 dependency on nuclear export (2020)

Introduction and hypotheses The purpose of this study was to uncover a novel targeted therapeutic approach for pancreatic ductal adenocarcinoma (PDAC). We previously discovered that keratin 17 (K17) is an independent negative prognostic biomarker for PDAC, where high K17 expression is associated with decreased patient survival. In our pre‐clinical mouse model, PDACs that overexpress K17 were four times more likely than controls to result in fatality within 7 weeks, suggesting that K17 drives tumor aggression. We determined that K17 functions as an oncoprotein by translocating into the nucleus of PDAC cells and enhances XPO‐1‐ mediated nuclear export and degradation of tumor suppressor proteins (TSPs). Here, we hypothesized that 1) K17 depends on nuclear export to drive tumor aggression and is highly sensitive to nuclear inhibition, compared to K17‐negative PDACs, and 2) blocking K17 enhanced XPO‐1‐mediated nuclear export causes enhanced apoptosis and cell cycle arrest. Methods and results To test the hypothesis that K17 depends on nuclear export to drive tumor aggression and is more sensitive to nuclear inhibition than K17‐negative PDACs, we performed pre‐clinical studies in mouse models and orthotopically implanted isogenic murine PDAC cells (LSL‐Kras G12D , LSL‐Trp53 R172H Pdx‐1‐Cre, KPC) that expressed human K17 (KPC‐K17) or not (KPC‐EV) in immunocompetent animals. After animal randomization, mice were treated three times weekly via oral gavage with selinexor, an inhibitor of the nuclear exporter, XPO‐1, that is currently in phase 2 clinical trials. We found that selinexor inhibited the growth of K17‐positive PDACs in mice, compared to K17‐negative PDACs, suggesting that K17sensitizes PDACs to selinexor treatment. To determine if this decreased tumor growth was due to a tumor‐cell nuclear export blockage, we performed in vitro studies and found that KPC‐K17 cells elicited a four‐fold increase in cell death and a two‐fold increase in G1/S cell cycle arrest compared to KPC‐EV cells. In addition, selinexor treatment led to nuclear retention of K17. To test the dependency of KPC‐K17 cells to K17‐mediated nuclear export, we challenged the cells to chemotherapeutic and targeted therapeutic agents that induce nuclear import inhibition (ivermectin), G1/S transition inhibition (palbociclib), and DNA‐damage (oxaliplatin). In contrast to selinexor treatment, there were no differences in cell death or cell cycle arrest between KPC‐K17 and KPC‐EV cells upon treatment with these compounds. Conclusions Our results suggest that K17‐positive tumors are specifically vulnerable to inhibition of nuclear export. Given that K17 expression is a biomarker that drives tumor aggression in PDACs, our results suggest that treatment with selinexor is a novel therapeutic opportunity for the most aggressive sub‐type of pancreatic cancer. Support or Funding Information Pancreatic Cancer Action Network
A Market for Unbiased Private Data: Paying Individuals According to\n their Privacy Attitudes (2012)

Since there is, in principle, no reason why third parties should not pay\nindividuals for the use of their data, we introduce a realistic market that\nwould allow these payments to be made while taking into account the privacy\nattitude of the participants. And since it is usually important to use unbiased\nsamples to obtain credible statistical results, we examine the properties that\nsuch a market should have and suggest a mechanism that compensates those\nindividuals that participate according to their risk attitudes. Equally\nimportant, we show that this mechanism also benefits buyers, as they pay less\nfor the data than they would if they compensated all individuals with the same\nmaximum fee that the most concerned ones expect.\n
Strätlingite formation in high-alumina cement — zeolite systems (1995)

Reaction mechanisms of strtitlingite formation in high-alumina cement (HAC)—zeolite systems were studied. A component separation method that made it possible to study individual reactions involving hydrated HAC and zeolite was employed. Different sodium salts, e.g. sodium silicate, sodium carbonate, sodium sulphate and sodium nitrate, were used to promote statlingite formation in the HAC paste. Strtitlingite forms preferentially to the cubic hydrogarnet phase in hydrated HAC systems in the presence of zeolite. A sufficiently high silicate concentration, arising from the dissolution of silicabearing materials such as zeolite, is required. A high pH environment is also conducive to stratlingite formation. The thermochemical stability of CAH 10 , the normal precursor to hydrogarnet formation, is apparently increased under the condition of high microsilica content.
Binder additives for warm mix asphalt technology (2013)

In determination of a material's coefficient of friction, the more common science used is known as tribology. Derived from the Greek tribo (to rub) and the Latin logia (study or learning), tribology is defined as the science and technology of interacting surfaces in relative motion. The coefficient of friction of a material has to be measured experimentally and cannot be calculated, which means it is empirical. Compared to smooth surfaces, rough surfaces like hot-mix aggregates tend to have higher coefficients. During production of asphalt mixtures, boundary fluids (like asphalt binders) can serve to reduce the coefficient of friction of aggregates. The concept of testing asphalt binders in thin films was first introduced by Reinke and Baumgardner at the Warm-Mix Technical Working Group (WMA TWG) in Baltimore, MD, December 2007; they suggested lubricity and internal friction reduction as a potential explanation of the mechanism which allows production of asphalt mixtures at reduced temperature - warm-mix asphalt (WMA). A continuation of the work of Reinke and Hanz is presented in this paper, moving from gap-dependent rheology to tribology utilizing a standard tribology fixture and new methods for testing asphalt binders using a dynamic shear rheometer. The following comprise this work: evaluations of various asphalts used to produce hot-mix asphalt (HMA) mixtures, as well as the effect they might have on friction characteristics, allowing production of warm-mix asphalt through non-chemical techniques, such as foaming; and regarding asphalt mixtures produced with Lubricity Optimized Asphalts TM (LOA), the evaluation of LOA and the effect additives have on friction characteristics.
Modeling the precedence effect for binaural sound source localization in noisy and echoic environments (2006)

We present a new way of modelling the Precedence Effect to enable the robust measurement of localization cues (ITD and IID) in echoic environments. Based on this we developed a localization system which is inspired by the auditory system of mammals. It uses a Gammatone filter bank for preprocessing and extracts the ITD cue via zero crossings (IID calculation is straight forward). The mapping between the cue values and the different angles is learned offline which facilitates the adaptation to different head geometries. The performance of the system is demonstrated by localization results for two simultaneous speakers and the mixture of a speaker, music, and fan noise in a normal meeting room. A real-time demonstrator of the system is presented in [1].
Abstract 3648: Targeting glypican-2 in neuroblastoma via single domain antibody-based immunotoxins and chimeric antigen receptor T cells (2017)

Abstract Neuroblastoma is the most common extracranial solid tumor in children. Approximately 45% of patients receiving standard therapy relapse and ultimately succumb to metastatic disease. One of the major challenges in the treatment of neuroblastoma and other pediatric cancers is the lack of effective targets. As such, there is an urgent need for a new therapeutic target. Here we demonstrate that glypican-2 (GPC2) protein is highly expressed in nearly half of neuroblastoma cases. High GPC2 expression has been correlated with poor overall survival when compared to patients with low GPC2 expression. The reduction of GPC2 expression inhibits neuroblastoma cell growth and induces tumor cell apoptosis through downregulation of Wnt/β-catenin signaling. We have discovered a group of human single domain antibodies specific for GPC2 and have used them to make two forms of antibody therapeutics, antibody-toxin conjugates (immunotoxins) and chimeric antigen receptor (CAR) T cells. Treatment with the immunotoxin inhibits proliferation of GPC2-positive neuroblastoma cells in vitro and mouse models. The CAR T cells targeting GPC2 suppress the growth of neuroblastoma xenograft tumors and eradicate disseminated neuroblastomas in mice. Our study establishes GPC2 as a new target of antibody-based cancer therapy and demonstrates that single domain-based antibody therapeutics can be used in the treatment of neuroblastoma. Citation Format: Nan Li, Haiying Fu, Stephen Hewitt, Dimiter Dimitrov, Javed Khan, Mitchell Ho. Targeting glypican-2 in neuroblastoma via single domain antibody-based immunotoxins and chimeric antigen receptor T cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3648. doi:10.1158/1538-7445.AM2017-3648
Properties of Electrodeposited CuSCN 2D Layers and Nanowires Influenced by Their Mixed Domain Structure (2014)

Electrodeposited copper thiocyanate (CuSCN) thin films and nanowires have been investigated by X-ray photoelectron spectroscopy (XPS), Raman, and optical spectroscopy. In addition, atomic force microscopy (AFM) together with scanning and transmission electron microscopy (SEM and TEM) have been employed for structural characterization. The multiple technique approach allows the correlation between structural, chemical, and electrical properties that are unique to the structure of this material. It has been found that CuSCN thin films and nanowires exhibit high crystalline quality with a close to stoichiometric composition. The XPS and Raman spectra suggest that the thiocyanate ion is bound to copper mainly through its S-end, with approximately 12–14% bound via the N-end. The applied absorption spectroscopy (Tauc and Urbach plots) points toward the possible coexistence of two large band gaps for the electrodeposited CuSCN. While its interpretation may be problematic from a purely physical perspective, we believe that this is a direct consequence of the occurrence of two CuSCN domains identified by XPS and Raman. A prominent absorption tail is observed that is assigned as either being due to the high concentration of the traps or a result of coexisting CuSCN domains. This absorption tail should not be an obstacle for the use of the copper thiocyanate in electronic devices, as the trap density could be reduced by annealing. In addition, nonannealed electrodeposited CuSCN thin films and nanowires of this type have recently been integrated into polymer solar cells and high efficiency has been obtained.
Coupling Reactions of Cephalosporin Sulfones:  A Stable 3-Stannylated Cephem (2001)

The first stable 3-metalated cephalosporin is reported and shown to be an excellent synthetic precursor to a number of prospective beta-lactamase inhibitors. Reaction: see text.
Apparatus for recording an audio signal with protection against re-recording thereof, and recording apparatus which indicates the presence of such protection (1993)

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An interactive belt-worn badge with a retractable string-based input mechanism (2013)

In this paper we explore a new type of wearable computing device, an interactive identity badge. An embedded LCD presents dynamic information to the wearer and interaction is facilitated by sensing movement of the retractable string which attaches the unit to the wearer's belt. This form-factor makes it possible to interact using a single hand, providing lightweight and immediate access to a variety of information when it's not convenient to pick up, unlock and interact directly with a device like a smartphone. In this paper we present our prototype interactive badge, demonstrate the underlying technology and describe a number of usage scenarios and interaction techniques
An AC magnetohydrodynamic micropump: towards a true integrated microfluidic system (1999)

An AC Magnetohydrodynamic (MHD) micropump has been demonstrated in which the Lorentz force is used to propel an electrolytic solution along a microchannel etched in silicon. This micropump has no moving parts, produces a continuous (not pulsatile) flow, and is compatible with solutions containing biological specimens. micropump, using the Lorentz force as the pumping mechanism for biological analysis. The AC Magnetohydrodynamic (MHD) micropump investigated produces a continuous flow and allows for complex microchannel design.
Solid-Phase Synthesis of the Lipopeptide Myr-HBVpreS/2-78, a Hepatitis B Virus Entry Inhibitor (2010)

Chronic HBV infection is the leading cause of liver cirrhosis and hepatocellular carcinoma (HCC). Synthetic peptides derived from the N-terminus of the large HBV envelope protein (L-protein) have been shown to efficiently block HBV entry. Myr-HBVpreS/2-78, the parent compound of these drugs, inhibits human HBV infection in vitro and in vivo. An efficient synthesis is required, as these peptides constitute a novel class of anti HBV drugs. Consequently, the solid phase synthesis of the N-terminal 77 amino acids of the viral L-protein was studied in detail. The peptide was N-terminally myristoylated to resemble the natural, postranslationally modified protein. The synthesis was monitored using the Fmoc cleavage pattern of the solid phase synthesis on a standard peptide synthesizer and by LC-MS analyses of the arising side products. “Difficult sequences” in the positions 42-47 of the peptide sequence complicate the efficient synthesis of the 77-mer peptide HBVpreS/2-78. Attempts were undertaken to optimize the synthesis by heating, double coupling or the use of pseudoproline dipeptides. HPLC-MS analyses showed that the efficiency of the synthesis could be increased best by temperature elevation. This resulted in a higher purity of the crude product after solid phase synthesis. It was possible to minimize the occurrence of side products due to the positive effects related to higher reaction temperature. In conclusion, the peptide is accessible by stepwise SPPS without the necessity of segment coupling.
Bit weaving: A non-prefix approach to compressing packet classifiers in TCAMs (2009)

Ternary Content Addressable Memories (TCAMs) have become the de facto standard in industry for fast packet classification. Unfortunately, TCAMs have limitations of small capacity, high power consumption, high heat generation, and high cost. The well-known range expansion problem exacerbates these limitations as each classifier rule typically has to be converted to multiple TCAM rules. One method for coping with these limitations is to use compression schemes to reduce the number of TCAM rules required to represent a classifier. Unfortunately, all existing compression schemes only produce prefix classifiers. Thus, they all miss the compression opportunities created by non-prefix ternary classifiers.
Focal-Plane Arrays of Quantum-Dot Infrared Photodetectors (2007)

Focal-plane arrays of semiconductor quantum-dot infrared photodetectors (QDIPs) are being developed as superior alternatives to prior infrared imagers, including imagers based on HgCdTe devices and, especially, those based on quantum-well infrared photodetectors (QWIPs). HgCdTe devices and arrays thereof are difficult to fabricate and operate, and they exhibit large nonunformities and high 1/f (where f signifies frequency) noise. QWIPs are easier to fabricate and operate, can be made nearly uniform, and exhibit lower 1/f noise, but they exhibit larger dark currents, and their quantization only along the growth direction prevents them from absorbing photons at normal incidence, thereby limiting their quantum efficiencies. Like QWIPs, QDIPs offer the advantages of greater ease of operation, greater uniformity, and lower 1/f noise, but without the disadvantages: QDIPs exhibit lower dark currents, and quantum efficiencies of QDIPs are greater because the three-dimensional quantization of QDIPs is favorable to the absorption of photons at normal or oblique incidence. Moreover, QDIPs can be operated at higher temperatures (around 200 K) than are required for operation of QWIPs. The main problem in the development of QDIP imagers is to fabricate quantum dots with the requisite uniformity of size and spacing. A promising approach to be tested soon involves the use of electron-beam lithography to define the locations and sizes of quantum dots. A photoresist-covered GaAs substrate would be exposed to the beam generated by an advanced, high-precision electron beam apparatus. The exposure pattern would consist of spots typically having a diameter of 4 nm and typically spaced 20 nm apart. The exposed photoresist would be developed by either a high-contrast or a low-contrast method. In the high-contrast method, the spots would be etched in such a way as to form steep-wall holes all the way down to the substrate. The holes would be wider than the electron beam spots perhaps as wide as 15 to 20 nm, but may be sufficient to control the growth of the quantum dots. In the low-contrast method, the resist would be etched in such a way as to form dimples, the shapes of which would mimic the electron-beam density profile. Then by use of a transfer etching process that etches the substrate faster than it etches the resist, either the pattern of holes or a pattern comprising the narrow, lowest portions of the dimples would be imparted to the substrate. Having been thus patterned, the substrate would be cleaned. The resulting holes or dimples in the substrate would serve as nucleation sites for the growth of quantum dots of controlled size in the following steps. The substrate would be cleaned, then placed in a molecular-beam-epitaxy (MBE) chamber, where native oxide would be thermally desorbed and the quantum dots would be grown.
Evaluation of Sulfur-Transfer Reagents for Large Scale Synthesis of Oligonucleotide Phosphorothioate Analogues (1997)

Abstract Several sulfur-transfer reagents have been evaluated for large scale synthesis of oligonucleotide phosphorothioate analogues, in which 3-ethoxy-1, 2-dithiazoline-5-one (EDITH, 5) shows potential as an alternative to Beaucage reagent.
A 6-way ring combiner/divider (2017)

A 6-way planar ring for combining/dividing signals is presented in this paper. Conventional planar power combining/dividing structures use derivatives of the Wilkinson combiner in a ladder like structure, or radial combiners. The ring combiner can be made smaller, provide higher port isolation, improved harmonic suppression and a single isolation port (e.g., delta output port), allowing energy harvesting in outphasing applications. The presented ring combiner achieves a measured insertion loss of <; 1dB from 5.5-5.8 GHz, while achieving > 25 dB isolation. The isolation notch is tunable by adjusting a static phase offset between the inputs. When linearly combining six, 26 dBm amplifiers, measurement results show 31dBm output. A 5-MHz, 64QAM LTE up-link signal is amplified without DPD and achieves an average out-put power of 24.1 dBm with an ACLR of >35 dBc. The power handling capability of the ring is only limited by the trace width and dielectric material, hence higher powers are achieveable.
Hypothalamic Arousal Regions Are Activated during Modafinil-Induced Wakefulness (2000)

Modafinil is an increasingly popular wake-promoting drug used for the treatment of narcolepsy, but its precise mechanism of action is unknown. To determine potential pathways via which modafinil acts, we administered a range of doses of modafinil to rats, recorded sleep/wake activity, and studied the pattern of neuronal activation using Fos immunohistochemistry. To contrast modafinil-induced wakefulness with spontaneous wakefulness, we administered modafinil at midnight, during the normal waking period of rats. To determine the influence of circadian phase or ambient light, we also injected modafinil at noon on a normal light/dark cycle or in constant darkness. We found that 75 mg/kg modafinil increased Fos immunoreactivity in the tuberomammillary nucleus (TMN) and in orexin (hypocretin) neurons of the perifornical area, two cell groups implicated in the regulation of wakefulness. This low dose of modafinil also increased the number of Fos-immunoreactive (Fos-IR) neurons in the lateral subdivision of the central nucleus of the amygdala. Higher doses increased the number of Fos-IR neurons in the striatum and cingulate cortex. In contrast to previous studies, modafinil did not produce statistically significant increases in Fos expression in either the suprachiasmatic nucleus or the anterior hypothalamic area. These observations suggest that modafinil may promote waking via activation of TMN and orexin neurons, two regions implicated in the promotion of normal wakefulness. Selective pharmacological activation of these hypothalamic regions may represent a novel approach to inducing wakefulness.
Phylogenetic Analysis of the Sigma 2 Protein Gene of Turkey Reoviruses (2004)

The open reading frame of the S3 segment encoding the σ2 protein of four turkey reovirus field isolates was analyzed for sequence heterogeneity. The turkey reoviruses we present here have a 97% amino acid identity to turkey NC 98. The S3 nucleotide and amino acid sequence similarity was ≤61% and 78%–80%, respectively, when compared to the chicken reovirus isolates. Comparison of amino acid sequences from chickens and turkeys with that of a duck isolate revealed a 53% and 55% similarity, respectively. Phylogenetic analyses, based on both nucleotide and amino acid sequence, resulted in three major groups among the avian reoviruses; these groups were clearly separated by species. The results of this study provide further evidence, based on the deduced σ2 sequence, that turkey reoviruses form a distinct, separate group relative to chicken and duck isolates. In addition, as a result of the limited sequence identity with their avian counterparts, turkey reoviruses could potentially be considered a separate virus species within subgroup 2 of the Orthoreovirus genus.
A unique and specific interaction between αT-catenin and plakophilin-2 in the area composita, the mixed-type junctional structure of cardiac intercalated discs (2007)

Alpha-catenins play key functional roles in cadherin-catenin cell-cell adhesion complexes. We previously reported on alphaT-catenin, a novel member of the alpha-catenin protein family. alphaT-catenin is expressed predominantly in cardiomyocytes, where it colocalizes with alphaE-catenin at the intercalated discs. Whether alphaT- and alphaE-catenin have specific or synergistic functions remains unknown. In this study we used the yeast two-hybrid approach to identify specific functions of alphaT-catenin. An interaction between alphaT-catenin and plakophilins was observed and subsequently confirmed by co-immunoprecipitation and colocalization. Interaction with the amino-terminal part of plakophilins appeared to be specific for the central ;adhesion-modulation' domain of alphaT-catenin. In addition, we showed, by immuno-electron microscopy, that desmosomal proteins in the heart localize not only to the desmosomes in the intercalated discs but also at adhering junctions with hybrid composition. We found that in the latter junctions, endogenous plakophilin-2 colocalizes with alphaT-catenin. By providing an extra link between the cadherin-catenin complex and intermediate filaments, the binding of alphaT-catenin to plakophilin-2 is proposed to be a means of modulating and strengthening cell-cell adhesion between cardiac muscle cells. This could explain the devastating effect of plakophilin-2 mutations on cell junction stability in intercalated discs, which lead to cardiac muscle malfunction.