gebhart/patrepeval huggingface dataset:
Oxadiazole-isopropylamides as Potent and Noncovalent Proteasome Inhibitors (2013)

Screening of the 50000 ChemBridge compound library led to the identification of the oxadiazole-isopropylamide 1 (PI-1833) which inhibited chymotrypsin-like (CT-L) activity (IC50 = 0.60 μM) with little effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L). LC-MS/MS and dialysis show that 1 is a noncovalent and rapidly reversible CT-L inhibitor. Focused library synthesis provided 11ad (PI-1840) with CT-L activity (IC50 = 27 nM). Detailed SAR studies indicate that the amide moiety and the two phenyl rings are sensitive toward modifications. Hydrophobic residues, such as propyl or butyl in the para position (not ortho or meta) of the A-ring and a m-pyridyl group as B-ring, significantly improve activity. Compound 11ad (IC50 = 0.37 μM) is more potent than 1 (IC50 = 3.5 μM) at inhibiting CT-L activity in intact MDA-MB-468 human breast cancer cells and inhibiting their survival. The activity of 11ad warrants further preclinical investigation of this class as noncovalent proteasome inhibitors.
Real-Time Gas Leak Detection and Quantification using Smart Cement (2020)

In this study, the highly sensing chemo-thermo-piezoresistive smart cement behavior as a function of temperature and pressure with a water-to-cement ratio of 0.38 was investigated. Series of quality control, curing, compression and high-pressure high-temperature (HPHT) lab experiments were performed to evaluate the smart cement behavior with pressure and temperature variations. Vipulanandan p-q curing model was used to predict the changes in resistivity with curing time. The piezoresistivity strain of smart cement after 1 day of curing under 140 °F was 207% which is much higher than the regular cement failure strain of 0.2%. The Vipulanandan p-q piezoresistivity model also predicted the experimental results successfully. Observed fluid loss and gas leak after 30 minutes of testing was recorded. The measured fluid loss was predicted using the Vipulanandan fluid loss model and compared to the API static fluid loss model. Smart cement detected and sensed gas leak throughout the fluid loss test. During the gas leak through the piezoresistive smart cement slurry, the resistivity change was positive which could be used as an indicator for immediate gas migration. During the gas leak in the smart cement slurry, the resistivity increase was about 36% at pressure gradient of 1,800 psi/ft for 70 °F curing. Vipulanandan fluid flow model, generalized Darcy's Law, predicted the non-linear responses of gas leak velocity (discharge per unit area) to the applied pressure gradient. Additionally, the electrical resistivity changes predicted the gas leak velocity in the smart cement at different curing temperatures.
A Performance Investigation of Adaptive Phase Estimations in Coherent Optical Communications (2011)

We carried out a comprehensive analysis to examine the phase error variances in three adaptive phase estimation (PE) methods: the adaptive decision-aided PE, the Kalman PE, and the normalized least-mean square PE algorithms. The results show that they share the same phase error variances but with different approaches to determine the stepsize. Their performances in different quadrature amplitude modulation formats are analytically investigated for the purpose of determining the laser linewidth tolerance. <?Pub _bookmark="" Command="[Quick Mark]"?>
Recovery of oil from Utah's Tar Sands. Final report, December 1, 1979-March 31, 1983 (1984)

Work was focused in the following main areas: water assisted extraction of bitumens, quality and disposal of tailings, and raw bitumen clean-up; thermal recovery of bitumens in a fluidized-bed characterization of bitumen obtained and coked sand combustion; recovery of heat from hot burned sand; upgrading of raw bitumens from water extraction and thermally produced bitumens including in situ recovered material. This report covers in particular the following: investigation of the effect of bitumen viscosity in hot water extraction of tar sands and bitumen concentrate cleaning and a study of the use of an air sparged hydroclone in bitumen recovery; thermal recovery of bitumen from two additional Utah tar sands: Tar Sand Triangle and Whiterocks; upgrading of tar sand bitumens by the processing sequences; coking followed by hydrotreating of product and hydropyrolysis followed by hydrotreating of product; experimental and theoretical studies of a fluidized-bed pyrolysis reactor with a coked sand combination reactor with transfer of heat from the combustor to the pyrolysis reactor by means of potassium filled heat pipe.
Data from Efficacy of the Antibody–Drug Conjugate W0101 in Preclinical Models of IGF-1 Receptor Overexpressing Solid Tumors (2023)

<div>Abstract<p>The insulin-like growth factor type 1 receptor (IGF-1R) is important in tumorigenesis, and its overexpression occurs in numerous tumor tissues. To date, therapeutic approaches based on mAbs and tyrosine kinase inhibitors targeting IGF-1R have only shown clinical benefit in specific patient populations. We report a unique IGF-1R–targeted antibody–drug conjugate (ADC), W0101, designed to deliver a highly potent cytotoxic auristatin derivative selectively to IGF-1R overexpressing tumor cells. The mAb (hz208F2-4) used to prepare the ADC was selected for its specific binding properties to IGF-1R compared with the insulin receptor, and for its internalization properties. Conjugation of a novel auristatin derivative drug linker to hz208F2-4 did not alter its binding and internalization properties. W0101 induced receptor-dependent cell cytotoxicity <i>in vitro</i> when applied to various cell lines overexpressing IGF-1R, but it did not affect normal cells. Efficacy studies were conducted in several mouse models expressing different levels of IGF-1R to determine the sensitivity of the tumors to W0101. W0101 induced potent tumor regression in certain mouse models. Interestingly, the potency of W0101 correlated with the expression level of IGF-1R evaluated by IHC. In an MCF-7 breast cancer model with high-level IGF-1R expression, a single injection of W0101 3 mg/kg led to strong inhibition of tumor growth. W0101 provides a potential new therapeutic option for patients overexpressing IGF-1R. A first-in-human trial of W0101 is currently ongoing to address clinical safety.</p></div>
TCB2, a new anti-human interleukin-2 antibody, facilitates heterodimeric IL-2 receptor signaling and improves anti-tumor immunity (2019)

IL-2 is a pleiotropic cytokine that plays an essential role in the survival, expansion, and function of CD8 T cells, regulatory T cells (Tregs), and natural killer (NK) cells. Previous studies showed that binding IL-2 with an anti-IL-2 monoclonal antibody (mAb) with a particular specificity could block its interaction with IL-2Rα, which is mainly expressed on Tregs. This selectivity can enhance the anti-tumor effects of IL-2 by activating CD8 T and NK cells, while disfavoring Treg stimulation. Based on this, we newly developed a series of anti-human IL-2 (hIL-2) mAbs (TCB1-3) that selectively stimulate CD8 T and NK cells without overtly activating Tregs. Among them, the hIL-2/TCB2 complex (hIL-2/TCB2c) exerted the best efficacy by inducing a prodigious expansion of host memory phenotype (MP) CD8 T (60-fold) and NK cells (18-fold) with less efficient Treg proliferation (5-fold). As a result, there was an average eightfold increase in the ratio of MP CD8 to Tregs. Accordingly, hIL-2/TCB2c strongly inhibited the growth of B16F10, MC38, and CT26 tumors. More remarkably, hIL-2/TCB2c showed synergy with checkpoint inhibitors such as anti-CTLA-4 or PD1 antibodies, and resulted in almost complete regression of implanted tumors and resistance to secondary tumor challenge. For direct clinical use, we generated a humanized form of TCB2 that had equal immunostimulatory and anti-tumor efficacy as a murine one. Collectively, these results show that TCB2 can provide a potent immunotherapeutic modality either alone or together with checkpoint inhibitors in cancer patients.
Understanding Discrete Facial Expressions in Video Using an Emotion Avatar Image (2012)

Existing video-based facial expression recognition techniques analyze the geometry-based and appearance-based information in every frame as well as explore the temporal relation among frames. On the contrary, we present a new image-based representation and an associated reference image called the emotion avatar image (EAI), and the avatar reference, respectively. This representation leverages the out-of-plane head rotation. It is not only robust to outliers but also provides a method to aggregate dynamic information from expressions with various lengths. The approach to facial expression analysis consists of the following steps: 1) face detection; 2) face registration of video frames with the avatar reference to form the EAI representation; 3) computation of features from EAIs using both local binary patterns and local phase quantization; and 4) the classification of the feature as one of the emotion type by using a linear support vector machine classifier. Our system is tested on the Facial Expression Recognition and Analysis Challenge (FERA2011) data, i.e., the Geneva Multimodal Emotion Portrayal-Facial Expression Recognition and Analysis Challenge (GEMEP-FERA) data set. The experimental results demonstrate that the information captured in an EAI for a facial expression is a very strong cue for emotion inference. Moreover, our method suppresses the person-specific information for emotion and performs well on unseen data.
A Probabilistic Graphical Model for Microphone Array Source Separation using Rich Pre-Trained Source Models (2006)

Voice based computing applications, such as phone communication and speech recognition, use microphone arrays to capture voice from a human speaker. In many environments of interest, however, sounds from other sources interfere with the speaker's voice, posing severe problems for subsequent processing. This paper describes a new framework for treating this problem, and presents and demonstrates a new algorithm for the cancellation of interfering sounds. Our framework combines techniques from statistical machine learning with ideas from speech and audio processing. An important feature involves training rich probabilistic models on data from different types of relevant sound sources. Those source models are then incorporated into a larger probabilistic model of the observed microphone data. Using that model we derive our algorithm, which is of the expectation-maximization type and infers from data the clean sound of separate individual sources. We report very good results on data recorded in different environments
A New Phenomenon: Sub-Tg, Solid-State, Plasticity-Induced Bonding in Polymers (2017)

Polymer self-adhesion due to the interdiffusion of macromolecules has been an active area of research for several decades. Here, we report a new phenomenon of sub-T<sub>g</sub>, solid-state, plasticity-induced bonding; where amorphous polymeric films were bonded together in a period of time on the order of a second in the solid-state at ambient temperatures, up to 60 K below their glass transition temperature (T<sub>g</sub>), by subjecting them to active plastic deformation. Despite the glassy regime, the bulk plastic deformation triggered the requisite molecular mobility of the polymer chains, causing interpenetration across the interfaces held in contact. Quantitative levels of adhesion and the morphologies of the fractured interfaces validated the sub-T<sub>g</sub>, plasticity-induced, molecular mobilization causing bonding. No-bonding outcomes (i) during the uniaxial compressive straining of films (a near-hydrostatic setting which strongly limits plastic flow) and (ii) between an 'elastic' and a 'plastic' film further established the explicit role of plastic deformation in this newly reported sub-T<sub>g</sub> solid-state bonding.
Closed-Loop Control of Local Magnetic Actuation for Robotic Surgical Instruments (2015)

We propose local magnetic actuation (LMA) as an approach to robotic actuation for surgical instruments. An LMA actuation unit consists of a pair of diametrically magnetized single-dipole cylindrical magnets, working as magnetic gears across the abdominal wall. In this study, we developed a dynamic model for an LMA actuation unit by extending the theory proposed for coaxial magnetic gears. The dynamic model was used for closed-loop control, and two alternative strategies-using either the angular velocity at the motor or at the load as feedback parameter-were compared. The amount of mechanical power that can be transferred across the abdominal wall at different intermagnetic distances was also investigated. The proposed dynamic model presented a relative error below 7.5% in estimating the load torque from the system parameters. Both the strategies proposed for closed-loop control were effective in regulating the load speed with a relative error below 2% of the desired steady-state value. However, the load-side closed-loop control approach was more precise and allowed the system to transmit larger values of torque, showing, at the same time, less dependence from the angular velocity. In particular, an average value of 1.5 mN·m can be transferred at 7 cm, increasing up to 13.5 mN·m as the separation distance is reduced down to 2 cm. Given the constraints in diameter and volume for a surgical instrument, the proposed approach allows for transferring a larger amount of mechanical power than what would be possible to achieve by embedding commercial dc motors.
NIMG-25IMPROVED LEAKAGE CORRECTION FOR DYNAMIC SUSCEPTIBILITY CONTRAST (DSC) PERFUSION MRI ESTIMATES OF RELATIVE CEREBRAL BLOOD VOLUME (rCBV) IN HIGH-GRADE GLIOMAS BY ACCOUNTING FOR BIDIRECTIONAL CONTRAST AGENT EXCHANGE (2015)

BACKGROUND: Contrast agent exchange through a compromised BBB results in imprecise estimates of rCBV using DSC-MRI. The current methods for leakage correction, however, are inaccurate in that they only account for leakage from the vascular to extravascular space. The current study explores a new bidirectional leakage model for DSC-MRI for improved rCBV estimates in high-grade gliomas. METHODS: The traditional model-based post-processing leakage correction algorithm that assumes unidirectional contrast agent extravasation (Boxerman-Weisskoff mode, BW-model) to account for bidirectional contrast eagent exchange between intra- and extravascular spaces (Bidir-model). We compared goodness of fit to raw leakage-contaminated relaxation rate curves and differences between modeld interstitial relaxation rate curves collected using DCE-MRI data from the same patients. We then compared the ability for both models to predict response to bevcizumab in recurrent GBMs. RESULTS: Using a mathematical simplification originally applied to DCE data we were able to obtain comparable computation times between the two techniques. The Bidir-model had significantly improved goodness of fit when compared with the BW-model in terms of both fit to raw, contaminated relaxation rate signals from DSC-MRI (P < 0.0001) as well as relaxation rate estimates in the interstitial space estimated using DCE-MRI (P = 0.0041). On average, enhancing tumor rCBV for the traditional BW-model was higher by 16.6%. Specifically, when the DSC signal is corrupted by T1-leakage the BW-model underestimates rCBV, and when then DSC signal is corrupted by T2*-leakage the traditional model overestimates rCBV. Results also suggests changes in rCBV calculated after bevacizumab using the Bidir-model significantly predicts overall survival (P = 0.03), whereas the traditional estimates of rCBV from the BW-model were not predictive. CONCLUSION: Inclusion of bidirectional exchange in the leakage correction model for DSC-MRI significantly improves the model fit to leakage-contaminated DSC-MRI data, significantly improves estimation of rCBV in gliomas, and improves biomarker accuracy for predicting response to anti-angiogenic therapy.
Properties of Novel Terahertz Electric Metamaterials (2007)

Planar electric metamaterials are studied with terahertz time-domain spectroscopy in transmission and reflection. Energy absorption of 5-20% due to Ohmic losses within the metal patterning is observed at resonant frequencies. Finite-element simulations verify experimental results.
A Potent, Long-Acting, Orally Active (2<i>R</i>)-2-[(1<i>R</i>)-3,3-Difluorocyclopentyl]-2-hydroxy-2-phenylacetamide:  A Novel Muscarinic M<sub>3</sub> Receptor Antagonist with High Selectivity for M<sub>3</sub> over M<sub>2</sub> Receptors (2000)

A novel series of (2R)-2-[(1R)-3, 3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamides was designed and synthesized based on the structure and biological profiles of an active metabolite 2 of our prototype muscarinic M(3) receptor selective antagonist 1, to develop a potent, long-acting, orally active M(3) antagonist for the treatment of urinary tract disorders, irritable bowel syndrome, and respiratory disorders. Investigation of (2R)-2-[(1R)-3, 3-difluorocyclopentyl]-2-hydroxy-2-phenylacetamides containing a phenyl or heterocyclic ring as the piperidinyl side chain in place of the 4-methyl-3-pentenyl moiety of 15a revealed that this acid moiety was a versatile template for improving the selectivity for M(3) over M(2) receptors in comparison with the corresponding cyclopentylphenylacetic acid group. However, since the in vitro metabolic stability of these analogues was insufficient compared with that of 2, further derivatization was performed by introducing an appropriate hydrophilic group into the phenyl or 2-pyridyl ring. Thus, the 1-(6-aminopyridin-2-ylmethyl)piperidine analogue 15y exhibiting 190-fold selectivity for M(3) receptors (K(i) = 2.8 nM) over M(2) receptors (K(i) = 530 nM) in a human binding assay and good in vitro metabolic stability in dog and human hepatic microsomes was identified. This compound has excellent oral activity at 4 h after oral dosing (1 mg/kg), inhibiting methacholine-induced bronchoconstriction in dogs, and may be useful in clinical situations in which M(3) over M(2) selectivity is desirable.
High Throughput Method of Extracting and Counting Strontium-90 in Urine (2016)

A method has been developed for the rapid extraction of Sr-90 from the urine of individuals exposed to radiation in a terrorist attack. The method employs two chromatographic ion-exchange materials: Diphonix resin and Sr resin, both of which are commercially available. The Diphonix resin reduces the alkali ion concentrations below 10 mM, and the Sr resin concentrates and decontaminates strontium-90. Experimental and calculational data are given for a variety of test conditions. On the basis of these results, a flowsheet has been developed for the rapid concentration and extraction of Sr-90 from human urine samples for subsequent beta-counting.
Crosstalk identification in xDSL systems (2001)

Crosstalk among telephone lines in the same or neighboring bundles is a major impairment in current xDSL systems. This paper proposes a novel idea of an impartial third party that identifies the crosstalk coupling functions among the twisted pairs in these xDSL systems. The crosstalk identification technique includes the following four major procedures: (1) the transmitted and received signals from each DSL modem for a predefined time period are collected and sent to the third party; (2) the signals are resampled according to the clock rate of the receiver of interest; (3) the signals' timing differences are estimated by cross correlation; and (4) the crosstalk coupling functions are estimated using the least-squares method. The performance of the cross correlation and least-squares methods is analyzed to determine the amount of data needed for identification. Simulation results show that the proposed methods can identify the crosstalk functions accurately and are consistent with theoretical analysis. These identified crosstalk functions can be used to significantly improve the data rate (e.g., multiuser detection) and to facilitate provisioning, maintenance, and diagnosis of the xDSL systems.
ChemInform Abstract: Large‐Scale and Facile Preparation of Pure Ammonia Borane Through Displacement Reactions. (2013)

Abstract Pure NH 3 BH 3 is prepared at the 100 g scale by displacement reactions of either NH 3 and Me 2 S·BH 3 with 94% yield, or NH 3 and Ph‐NMe 2 ·BH 3 with 91% yield, with both reactions performed in toluene at room temperature.
ChemInform Abstract: Cholecystokinin Antagonists. Synthesis and Biological Evaluation of 4‐Substituted 4H‐(1,2,4)Triazolo(4,3‐a)(1,4)benzodiazepines. (1988)

Abstract The thioketones (I), prepared from the corresponding ketones with Lawesson's reagent, react with hydrazine (II) to give the hydrazones (III) which undergo cyclocondensation with the orthoesters (IV) to form the triazolobenzodiazepines (V).
Functional Activity of Antibodies Directed towards Flagellin Proteins of Non-Typhoidal Salmonella (2016)

Non-typhoidal Salmonella (NTS) serovars Typhimurium and Enteritidis are major causes of invasive bacterial infections in children under 5 years old in sub-Saharan Africa, with case fatality rates of ~20%. There are no licensed NTS vaccines for humans. Vaccines that induce antibodies against a Salmonella Typhi surface antigen, Vi polysaccharide, significantly protect humans against typhoid fever, establishing that immune responses to Salmonella surface antigens can be protective. Flagella proteins, abundant surface antigens in Salmonella serovars that cause human disease, are also powerful immunogens, but the functional capacity of elicited anti-flagellar antibodies and their role in facilitating bacterial clearance has been unclear. We examined the ability of anti-flagellar antibodies to mediate microbial killing by immune system components in-vitro and assessed their role in protecting mice against invasive Salmonella infection. Polyclonal (hyperimmune sera) and monoclonal antibodies raised against phase 1 flagellin proteins of S. Enteritidis and S. Typhimurium facilitated bacterial uptake and killing of the homologous serovar pathogen by phagocytes. Polyclonal anti-flagellar antibodies accompanied by complement also achieved direct bacterial killing. Serum bactericidal activity was restricted to Salmonella serovars expressing the same flagellin used as immunogen. Notably, individual anti-flagellin monoclonal antibodies with complement were not bactericidal, but this biological activity was restored when different monoclonal anti-flagellin antibodies were combined. Passive transfer immunization with a monoclonal IgG antibody specific for phase 1 flagellin from S. Typhimurium protected mice against lethal challenge with a representative African invasive S. Typhimurium strain. These findings have relevance for the use of flagellin proteins in NTS vaccines, and confirm the role of anti-flagellin antibodies as mediators of protective immunity.
Interference-aware multi-iterative equalization and detection for frequency-selective MIMO channels (2016)

Turbo equalization has demonstrated to be a powerful approach for wireless transmission over frequency-selective channels introducing intersymbol interferences (ISI). Regarding multiple-input multiple-output (MIMO) systems, tree-search based MIMO detection techniques (e.g., sphere detection) are well suited for significantly reducing multi-antenna interferences. However, direct application of these detection techniques under the presence of ISI leads to vast processing complexity, increasing exponentially with the channel length and the number of transmitting antennas. In this paper, a low-complex two-stage approach is described splitting the interference reduction into a frequency-domain equalization stage and a time-domain sphere detection stage. Both are able to take a-priori information into account. Based on this, we derive a novel multi-iterative receiver, enabling powerful and adaptable processing with respect to the dominating interferences.