gebhart/patrepeval huggingface dataset:
Abstract 1791: CO-1686, a novel mutant-selective EGFR inhibitor, overcomes T790M mediated resistance in Non-Small Cell Lung Cancer (NSCLC) (2012)

Abstract Introduction: Non-small cell lung cancer (NSCLC) patients with activating EGFR mutations initially respond well to the EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. However, clinical efficacy is limited by the development of resistance. The most common mechanism of resistance is a second site mutation within exon 20 of EGFR (T790M), observed in ∼50% of cases. CO-1686 is an irreversible kinase inhibitor that targets the mutant forms of EGFR by inhibiting the common activating mutations (L858R, delE746-A750) and the gatekeeper mutation (T790M) but not the wild-type receptor. Therefore, CO-1686 has the potential to effectively treat first- and second-line NSCLC patients with EGFR mutations without causing the dose limiting toxicities associated with approved EGFR kinase inhibitors or those in clinical development. Experimental procedures: Using structure-based drug design, CO-1686, a covalent, irreversible small molecule, which selectively inhibits mutant EGFR, was identified. CO-1686 potency was assessed against four common EGFR mutations (L858R, delE746-A750, L858R/T790M and delE746-A750/T790M) using in vitro biochemical and cell-based assays. Antitumor activity of CO-1686 as a single agent was assessed in NSCLC xenograft models harboring EGFR mutations: H1975 (L858R/T790M) and HCC827 (delE746-A750). Pharmacodynamic studies were performed to evaluate effects on cell survival and EGFR signaling. Results: In vitro and in vivo pharmacology studies focused on evaluating CO-1686 potency in four EGFR mutations common in NSCLC patients: L858R, delE746-A750, L858R/T790M and delE746-A750/T790M. CO-1686 was shown to be active against all four EGFR mutants. Effects of CO-1686 on cell proliferation and EGFR signaling were evaluated in HCC827 cells (delE746-A750) and its erlotinib-resistant clone, HCC827-EPR harboring the second site mutation T790M (delE746-A750/T790M). CO-1686 inhibited cell proliferation in both cell lines equally (GI50 values of 12 nM in the parental line and 19 nM in the T790M-positive clone). In mouse xenograft studies, oral dosing of CO-1686 in H1975 double mutant (L858R/T790M) and in HCC827 single mutant (delE746-A750) models caused tumor shrinkage as a single agent in a dose-dependent manner. Different dosing schedules were explored. Conclusions: Our results establish CO-1686 as a potent, mutant-selective EGFR inhibitor with excellent in vivo activity in mice bearing tumors with activating EGFR mutations as well as the resistance mutation T790M. These data suggest that treatment with CO-1686 as a single agent can overcome T790M-mediated drug resistance in NSCLC. Initially, clinical development will focus on NSCLC patients with mutant EGFR. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1791. doi:1538-7445.AM2012-1791
Waveguide And Diffractive Coupling Eleaments For Optoelectronic Packaging (1993)

Optoelectronics continues to make inroads into computer and signal processing systems requiring high speed interconnection networks. While optical fibers predominate as the interconnect for long path lengths, at lower levels within an electronic system optical waveguides may be used as an interconnect media for signal distribution. Signal distribution using waveguides also implies input/output coupling and the need to redistribute an optical signal within the plane of the waveguide. For the latter, diffractive elements may be used for inplane and out-of-plane signal distribution. Diffractive coupling/signal distribution elements are attractive because of their directional properties and potential manufacturability.
PRE-CLINICAL ASSESSMENT OF GENZ-29155, A NOVEL SMALL MOLECULE INHIBITOR OF APOPTOSIS WITH ANTI-REJECTION EFFECTS IN NON-HUMAN PRIMATES. (2008)

Kirk, A; Weaver, T; Charafeddine, A; Leopardi, F; Agarwal, A; Batty, D S.; Williams, J; Nahill, S Author Information
Bushen Yijing Fang Reduces Fall Risk in Late Postmenopausal Women with Osteopenia: A Randomized Double-blind and Placebo-controlled Trial (2019)

Falls in late postmenopausal women with osteopenia usually cause fractures with severe consequences. This 36-month randomized, double-blind and placebo-controlled trial with a 10-year observational follow-up study aimed to investigate the long-term effect of herbal formula Bushen Yijing Fang (BSYJF) on fall risk in the late postmenopausal women with osteopenia. 140 late postmenopausal women (Femoral neck T-score, -2.5~-2 SD) were recruited and randomized to orally receive calcium carbonate 300 mg daily with either BSYJF or placebo for 36 months. The effect was further investigated for another 10-year follow-up. During the 36-month administration, there were 12 falls in BSYJF group and 28 falls in placebo group, respectively, indicating 64% lower risk of falls (RR 0.36 [95% CI, 0.18 to 0.71]; P = 0.004) in BSYJF group. During the 10-year follow-up, 36% lower fall risk (RR 0.64 [95% CI, 0.46 to 0.89]; P = 0.009) was observed in BSYJF group. No significant difference was found in safety profile between two groups. Thirty-six-month administration of BSYJF reduced fall risk with an increase in bone mass, and its latent effect on fall risk was continually observed in the 10-year follow-up in late postmenopausal women with osteopenia. This clinical trial was registered at Chinese clinical trial registry (ChiCTR-IOR-16008942).
Effects on Aqueous Flow of Dorzolamide Combined with Either Timolol or Acetazolamide (2004)

The combination of dorzolamide and timolol demonstrated significant aqueous flow additivity and had greater IOP efficacy than the combination of dorzolamide and acetazolamide.
Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6 (2016)

Up to 30% of patients with acute myeloid leukemia have constitutively activating internal tandem duplications (ITDs) of the FLT3 receptor tyrosine kinase. Such mutations are associated with a poor prognosis and a high propensity to relapse after remission. FLT3 inhibitors are being developed as targeted therapy for FLT3-ITD(+) acute myeloid leukemia; however, their use is complicated by rapid development of resistance, which illustrates the need for additional therapeutic targets. We show that the US Food and Drug Administration-approved CDK4/6 kinase inhibitor palbociclib induces apoptosis of FLT3-ITD leukemic cells. The effect is specific for FLT3-mutant cells and is ascribed to the transcriptional activity of CDK6: CDK6 but not its functional homolog CDK4 is found at the promoters of the FLT3 and PIM1 genes, another important leukemogenic driver. There CDK6 regulates transcription in a kinase-dependent manner. Of potential clinical relevance, combined treatment with palbociclib and FLT3 inhibitors results in synergistic cytotoxicity. Simultaneously targeting two critical signaling nodes in leukemogenesis could represent a therapeutic breakthrough, leading to complete remission and overcoming resistance to FLT3 inhibitors.
Data-Driven Multiobjective Controller Optimization for a Magnetically Levitated Nanopositioning System (2020)

The performance achieved with traditional model-based control system design approaches typically relies heavily on accurate modeling of the motion dynamics. However, modeling the true dynamics of present-day increasingly complex systems can be an extremely challenging task; and the usually necessary practical approximations often renders the automation system to operate in a nonoptimal condition. This problem can be greatly aggravated in the case of a multiaxis magnetically levitated (maglev) nanopositioning system where the fully floating behavior and multiaxis coupling make extremely accurate identification of the motion dynamics largely impossible. On the other hand, in many related industrial automation applications, e.g., the scanning process with the maglev system, repetitive motions are involved which could generate a large amount of motion data under nonoptimal conditions. These motion data essentially contain rich information; therefore, the possibility exists to develop an intelligent automation system to learn from these motion data, and to drive the system to operate toward optimality in a data-driven manner. Along this line then, this article proposes a data-driven model-free controller optimization approach that learns from the past nonoptimal motion data to iteratively improve the motion control performance. Specifically, a novel data-driven multiobjective optimization approach is proposed that is able to automatically estimate the gradient and Hessian purely based on the measured motion data; the multiobjective cost function is suitably designed to take into account both smooth and accurate trajectory tracking. In this article, experiments are then conducted on the maglev nanopositioning system to demonstrate the effectiveness of the proposed method, and the results show rather clearly the practical appeal of our methodology for related complex robotic systems with no accurate model available.
Lipid–porphyrin vesicles: morphology and O2binding in aqueous medium (1993)

Amphilphilic tetraphenylporphin derivatives having four dialkylglycerophosphocholine groups on the ring plane (lipid-porphyrins) form spherical unilamellar vesicles of diameter ca. 100 nm in water; the vesicles composed of lipid–porphyrinatoiron(II)–1-dodecylimidazole (DIm), can bind dioxygen reversibly in aqueous medium.
Effect of the Stirring during the Hydrothermal Synthesis of C-LiFePO4 (2014)

We report that the rotation speed of the stirring in the hydrothermal reactor process is an important parameter that affects the structural properties and the electrochemical performance of LiFePO 4 . The best results are obtained for a rotation speed of 280 revolutions per minute. It is argued that this improved performance is related to the optimized morphology of the particles, and a smaller agglomeration of the particles. Since this material meets a worldwide success as a positive electrode for commercial Li-ion batteries.
Recognition of ballet micro-movements for use in choreography (2013)

Computer vision as an entire field has a wide and diverse range of applications. The specific application for this project was in the realm of dance, notably ballet and choreography. This project was proof-of-concept for a choreography assistance tool used to recognize and record dance movements demonstrated by a choreographer. Keeping the commercial arena in mind, the Kinect from Microsoft was chosen as the imaging hardware, and a pilot set chosen to verify recognition feasibility. Before implementing a classifier, all training and test data was transformed to a more applicable representation scheme to only pass the important aspects to the classifier to distinguish moves for the pilot set. In addition, several classification algorithms using the Nearest Neighbor (NN) and Support Vector Machine (SVM) methods were tested and compared from a single dictionary as well as on several different subjects. The results were promising given the framework of the project, and several new expansions of this work are proposed.
In situdoping of catalyst-free InAs nanowires (2012)

We report on in situ doping of InAs nanowires grown by metal-organic vapor-phase epitaxy without any catalyst particles. The effects of various dopant precursors (Si(2)H(6), H(2)S, DETe, CBr(4)) on the nanowire morphology and the axial and radial growth rates are investigated to select dopants that enable control of the conductivity in a broad range and that concomitantly lead to favorable nanowire growth. In addition, the resistivity of individual wires was measured for different gas-phase concentrations of the dopants selected, and the doping density and mobility were extracted. We find that by using Si(2)H(6) axially and radially uniform doping densities up to 7 × 10(19) cm(-3) can be obtained without affecting the morphology or growth rates. For sulfur-doped InAs nanowires, we find that the distribution coefficient depends on the growth conditions, making S doping more difficult to control than Si doping. Moreover, above a critical sulfur gas-phase concentration, compensation takes place, limiting the maximum doping level to 2 × 10(19) cm(-3). Finally, we extract the specific contact resistivity as a function of doping concentration for Ti and Ni contacts.
Disabling the Nuclear Translocalization of RelA/NF-κB by a Small Molecule Inhibits Triple-Negative Breast Cancer Growth (2021)

Our study demonstrates that CRL1101 may lead to new NF-κB-targeted therapeutics for TNBC. Further, blocking of nuclear translocation of shuttling transcription factors may be a useful general strategy in cancer drug development.
Species-Specific Inhibition of RIG-I Ubiquitination and IFN Induction by the Influenza A Virus NS1 Protein (2012)

Influenza A viruses can adapt to new host species, leading to the emergence of novel pathogenic strains. There is evidence that highly pathogenic viruses encode for non-structural 1 (NS1) proteins that are more efficient in suppressing the host immune response. The NS1 protein inhibits type-I interferon (IFN) production partly by blocking the TRIM25 ubiquitin E3 ligase-mediated Lys63-linked ubiquitination of the viral RNA sensor RIG-I, required for its optimal downstream signaling. In order to understand possible mechanisms of viral adaptation and host tropism, we examined the ability of NS1 encoded by human (Cal04), avian (HK156), swine (SwTx98) and mouse-adapted (PR8) influenza viruses to interact with TRIM25 orthologues from mammalian and avian species. Using co-immunoprecipitation assays we show that human TRIM25 binds to all tested NS1 proteins, whereas the chicken TRIM25 ortholog binds preferentially to the NS1 from the avian virus. Strikingly, none of the NS1 proteins were able to bind mouse TRIM25. Since NS1 can inhibit IFN production in mouse, we tested the impact of TRIM25 and NS1 on RIG-I ubiquitination in mouse cells. While NS1 efficiently suppressed human TRIM25-dependent ubiquitination of RIG-I 2CARD, NS1 inhibited the ubiquitination of full-length mouse RIG-I in a mouse TRIM25-independent manner. Therefore, we tested if the ubiquitin E3 ligase Riplet, which has also been shown to ubiquitinate RIG-I, interacts with NS1. We found that NS1 binds mouse Riplet and inhibits its activity to induce IFN-b in murine cells. Furthermore, NS1 proteins of human but not swine or avian viruses were able to interact with human Riplet, thereby suppressing RIG-I ubiquitination. In conclusion, our results indicate that influenza NS1 protein targets TRIM25 and Riplet ubiquitin E3 ligases in a species-specific manner for the inhibition of RIG-I ubiquitination and antiviral IFN production.
Comparative Analysis of CHATGPT and the evolution of language models (2023)

Interest in Large Language Models (LLMs) has increased drastically since the emergence of ChatGPT and the outstanding positive societal response to the ease with which it performs tasks in Natural Language Processing (NLP). The triumph of ChatGPT, however, is how it seamlessly bridges the divide between language generation and knowledge models. In some cases, it provides anecdotal evidence of a framework for replicating human intuition over a knowledge domain. This paper highlights the prevailing ideas in NLP, including machine translation, machine summarization, question-answering, and language generation, and compares the performance of ChatGPT with the major algorithms in each of these categories using the Spontaneous Quality (SQ) score. A strategy for validating the arguments and results of ChatGPT is presented summarily as an example of safe, large-scale adoption of LLMs.
Predictive models of short- and long-term survival in patients with nonbiliary cirrhosis (2003)

The limited number of donor organs has placed a burden on the medical community to improve patient selection and timing of liver transplantation (LT). We aim to evaluate short- and long-term survival of 124 consecutive patients with a diagnosis of nonbiliary cirrhosis. Seventeen clinical, biochemical, functional, and hemodynamic parameters were computed. Patient survival was evaluated in the short term (3 months) by logistic regression, and the predictive power of the model was evaluated using receiver operating characteristic curves and the log likelihood ratio. For the long-term (up to 5 years) prognosis, the Cox proportional model was used. During follow-up, 54 patients died and 20 patients underwent LT. In the short-term study, the Model for End-Stage Liver Disease score (including bilirubin level, international normalized ratio [INR], and creatinine level) was as predictive as our score, which contained only two independent indicators (bilirubin and creatinine levels). In the long-term study, three independent variables (albumin level, INR, and creatinine level) emerged from the Cox model, and patients were classified into three survival-risk groups according to a prognostic index (PI): -1.039 x albumin (grams per deciliter) + 1.909 x log(e) INR + 1.207 x log(e) serum creatinine (milligrams per deciliter). Survival probabilities at 1 and 5 years were 89% and 80%, 63% and 52%, and 23% and 10% with a low, medium, and high PI, respectively. The validation study using the split-sample technique and data from independent patients confirmed that a high PI (>-2.5) identifies patients with a poor prognosis within 5 years. We thus have shown and validated that risk for death at the short and long term of patients with nonbiliary cirrhosis can be predicted with great accuracy using models containing a few simple and easily obtained objective variables, and these survival models are useful tools in clinical decision making, especially in deciding to list patients for LT and prioritization on the liver waiting list.
GSTT1 a s aprognosticato rfo rrecurrenc eand progression in patients with non-muscle-invasive bladder cancer (2010)

Although polymorphisms in glutathione S-transferase (GST) have been associated with the risk of bladder cancer (BC), few reports provide information about the development of BC. The aim of the present study was to investigate the effect of homozygous glutathione S-transferase-µ (GSTM1) and glutathione S-transferase-� (GSTT1) deletions as prognostic markers in non-muscle-invasive bladder cancer (NMIBC). A total of 241 patients with primary NMIBC were enrolled in this study. GSTM1 and GSTT1polymorphisms were analyzed by multiplex polymerase chain reaction (PCR) using blood genomic DNA. The results were compared with clinicopathological parameters. The prognostic significance of the GSTs was evaluated by Kaplan-Meier and multivariate Cox regression model. A statistically significant association between genotype and histopathological parameter was not observed. The patients with the GSTT1-positive genotype had significantly reduced recurrence- and progression-free survival than those with the GSTT1-null genotype (log-rank test, p < 0.05, respectively). Recurrence- and progression-free survival were not related to the GSTM1 genotypes. In multivariate regression analysis, the GSTT1-positive genotype was the independent predictor for recurrence (hazard ratio (HR), 1.631; p = 0.043) and progression (HR, 3.418; p = 0.006). These results suggested that the GSTT1 genotype could be a useful prognostic marker for recurrence and progression in NMIBC.
Snooze (2011)

Increasingly, mobile devices equipped with 802.11n interfaces are being used for a wide variety of applications including bandwidth-intensive HD video streaming. Recent work has shown that 802.11n interfaces are power-hungry, so energy management is an important challenge. 802.11n implementations have additional power states relative to earlier generations of 802.11 technology, so energy management challenges for 802.11n are qualitatively different compared to that faced by prior work. In this paper, we describe the design and implementation of Snooze, an energy management technique for 802.11n which uses two novel and inter-dependent mechanisms: client micro-sleeps and antenna configuration management. In Snooze, the APmonitors traffic on the WLAN and directs client sleep times and durations as well as antenna configurations, without significantly affecting throughput or delay. Snooze achieves 30~85% energy-savings over CAM across workloads ranging from VoIP and video streaming to file downloads and chats.
Direct comparison of Mössbauer and channeling studies of implanted119sn in silicon single crystals (1975)

Abstract Mössbauer parameters, measured with a resonance counter, have been compared with channeling results on the same samples, for ′119mSn implanted into silicon single crystals. The implantation dose was varied between ∼1014 and ∼1017 atoms/cm2, for target temperatures of 2O°C and 400°C. The channeling results in hot implants show that Sn is embedded substitutionally, and the Mössbauer parameters are nearly dose independent in the range indicated above. Except for a very low-dose implant (∼1013 atoms/cm2) the room-temperature implants lead to complete damage (no channeling dip) and significantly different Mössbauer parameters. Subsequent annealing at 700°C, however, leads to values close to those characteristic of hot implants. The small dose dependence for hot implants, even for doses leading to ∼80% damage, as measured by channeling, indicates that the microscopic ordering is preserved.
Impact of Stereospecific Intramolecular Hydrogen Bonding on Cell Permeability and Physicochemical Properties (2014)

Profiling of eight stereoisomeric T. cruzi growth inhibitors revealed vastly different in vitro properties such as solubility, lipophilicity, pKa, and cell permeability for two sets of four stereoisomers. Using computational chemistry and NMR spectroscopy, we identified the formation of an intramolecular NH→NR3 hydrogen bond in the set of stereoisomers displaying lower solubility, higher lipophilicity, and higher cell permeability. The intramolecular hydrogen bond resulted in a significant pKa difference that accounts for the other structure-property relationships. Application of this knowledge could be of particular value to maintain the delicate balance of size, solubility, and lipophilicity required for cell penetration and oral administration for chemical probes or therapeutics with properties at, or beyond, Lipinski's rule of 5.
Semi-direct EKF-based monocular visual-inertial odometry (2015)

We propose a novel monocular visual inertial odometry algorithm that combines the advantages of EKF-based approaches with those of direct photometric error minimization methods. The method is based on sparse, very small patches and incorporates the minimization of photometric error directly into the EKF measurement model so that inertial data and vision-based surface measurements are used simultaneously during camera pose estimation. We fuse vision-based and inertial measurements almost at the raw-sensor level, allowing the estimated system state to constrain and guide image-space measurements. Our formulation allows for an efficient implementation that runs in real-time on a standard CPU and has several appealing and unique characteristics such as being robust to fast camera motion, in particular rotation, and not depending on the presence of corner-like features in the scene. We experimentally demonstrate robust and accurate performance compared to ground truth and show that our method works on scenes containing only non-intersecting lines.
Dosimetry of a D2/D3 dopamine receptor antagonist that can be used with PET or SPECT. (1995)

The data suggest that FIDA-2 can be used to produce relatively high contrast images of the D2/D3 dopaminergic system with substantially less than the maximum allowable radiation dose for research volunteers.