gebhart/patrepeval huggingface dataset:
Mutational Analysis of the Endothelin Type A Receptor (ETA):  Interactions and Model of the Selective ETAAntagonist BMS-182874 with the Putative ETAReceptor Binding Cavity (1996)

Endothelin (ET) receptor antagonism is a potential therapeutic intervention in the treatment of vascular diseases. To elucidate the mechanism of antagonist-ET receptor complex formation, the interactions of four chemically distinct antagonists were investigated using a combination of genetic and biochemical approaches. By site-specific mutagenesis we previously demonstrated that Tyr129 in the second transmembrane domain was critical for high-affinity, subtype-selective binding to the A subtype of ET (ETA) receptors [Krystek et al. (1994) J. Biol. Chem. 269, 12383-12386]. Affinities of the constrained cyclic pentapeptide BQ-123, the pyrimidinylbenzenesulfonamide bosentan, the indancarboxlic acid SB 209670, and the naphthalenesulfonamide BMS-182874 were decreased 20-1000-fold in Tyr129Ala, Tyr129Ser, and Tyr129His ETA receptor mutants. Substitution of Tyr129 with Phe or Trp did not alter the high-affinity binding of BQ-123, bosentan, or SB 209670. BMS-182874 binding affinity was decreased 10-fold in Tyr129Phe and Tyr129trp ET receptors. These data indicate a role of aromatic interactions in the binding of these antagonists to ETA receptors an, in the case of BMS-182874, also suggested a hydrogen bond with the tyrosine hydroxyl. This hypothesis was supported by structure-activity data with analogs of BMS-182874 that varied the C-5 dimethylamino substituent on the naphthalene ring. Mutation of Asp126 and Asp133 also altered binding of BMS-182874 and C-5 analogs. In all cases, naphthalenesulfonamide binding was more severely affected by mutation of Asp133 than by mutation of Asp126. Phosphoinositide hydrolysis and extracellular acidification rate studies demonstrated the importance of Tyr129 to ETA-mediated signal transduction. On the basis of these data, two plausible models of the docked conformation of BMS-182874 in the ETA receptor are proposed as a starting point for further delineation of interactions that underlie antagonist-ETA receptor complex formation.
The Luminescent Process in Organic Light Emitting Devices (2005)

Understanding the electroluminescent (EL) process in organic light emitting devices is very important for the rational design of optimized chromophores for use in organic LEDs. By comparing solution and solid state fluorescence spectra, it has been shown that molecularly localized or Frenkel excitons are responsible for the EL output.
COBALT AND CHROMIUM LEVELS FOLLOWING METAL-ON-METAL HIP RESURFACING WITH THE CORMET 2000 PROSTHESIS (2009)

Introduction: Metal-on-metal (MOM) hip resurfacing releases ions locally and into the systemic circulation, raising concern for potential long term complications of elevated trace metals. This study was designed to monitor serum cobalt (Co) and chromium (Cr) levels in patients after MOM resurfacing hip arthroplasty with the Cormet 2000 prosthesis and to compare detected levels with those previously reported for hip resurfacing prostheses. Methods: We prospectively followed patients receiving the Cormet 2000 device. Serum samples were collected at 6 months, 1, 2, and 3 years following surgery. Pre-operative controls were obtained from subjects without implants. Serum Co/Cr levels were determined using high-resolution inductively coupled plasma mass spectrometry. ANOVA was used to compare ion levels in each group. Statistical significance was set at p Results: 40 subjects (25 male) were followed. Average age was 51 years (33.7–66.1). Median preoperative Co/ Cr levels were 0.27 microg/L (0.087–0.601) and 0.19 (0.014–0.576), respectively. Co/Cr levels were significantly increased at all time points when compared to preoperative levels (p Conclusion: Elevated serum Co/Cr levels were observed at all time points following implantation. Continued elevations at three years were observed; however, the levels appear to be trending down suggestive of a “wear-in” period. Long term elevations of Co/Cr levels are concerning and will require additional studies to assess long term health risks of these levels in this population.
Enantioselective Synthesis of Brinzolamide (AL-4862), a New Topical Carbonic Anhydrase Inhibitor. The “DCAT Route” to Thiophenesulfonamides (1999)

A large scale synthesis of the topical carbonic anhydrase inhibitors AL-4623A (13a·HCl) and AL-4862 (13b) from 3-acetyl-2,5-dichlorothiophene (“DCAT”, 1) is described. Reaction of 1 with NaSBn gave thioether 2, which was converted via sulfenyl chloride 3 and sulfenamide 5 to sulfonamide 6. Bromination of 6 gave bromo ketone 7, which upon reduction with (+)-B-chlorodiisopinocampheylborane and cyclization of the resulting bromohydrin produced S thieno[3,2-e]-1,2-thiazine 8a (96% ee) after chromatography. Treatment of 8a in THF with n-BuLi at −70 °C resulted in Li−Cl exchange. Reaction of the thienyllithium with SO2 and hydroxylamine O-sulfonic acid afforded bis-sulfonamide 11a. Protection of 11a as the acetimidate 12a, followed by tosylation and amination, gave R amine 13a. The synthesis of 13b proceeded via primary sulfonamide 16, which was brominated, reduced, and cyclized to give S thieno[3,2-e]-1,2-thiazine 18 (>98% ee). By virtue of the ionizable NH, 18 was separable from reduction byproducts by base extraction. Alkylation of 18 with 3-bromopropyl methyl ether afforded 8b, which was converted as above, via 11b, to AL-4862 (13b). These procedures provided multihundred gram lots of 13a and 13b.
Deep Hierarchical Reinforcement Learning for Autonomous Driving with Distinct Behaviors (2018)

Deep reinforcement learning has achieved great progress recently in domains such as learning to play Atari games from raw pixel input. The model-free characteristics of reinforcement learning free us from hand-encoding complex policies. However, for real world tasks such as autonomous driving, there are some complex sequential decision making processes that contain distinct behaviors. Due to the delayed rewards and the averaged gradient, it is pretty difficult for a flat deep reinforcement learning algorithm to learn a good policy. In this paper, we design a hierarchical neural network policy and propose a hierarchical policy gradient method to train the network with the semi markov decision process (SMDP) temporal abstraction formulation. We apply this method to a traffic light passing scenario in autonomous driving, where the vehicle has two distinct behaviors (e.g., pass and stop) and its primitive actions (e.g., acceleration) should follow the corresponding behavior. We show via simulation that our method is able to select correct decision and acts appropriately when the traffic light turns yellow. On the contrary, the flat reinforcement learning algorithm is not able to achieve a good performance and exhibits a large variance. Furthermore, the trained neural network modules are reusable in the future to cover more scenarios.
Abstract 4884: OXPHOS: A novel target for cancer therapy in oncogene addicted tumor (2018)

Abstract Cancer cells are highly dependent on glycolysis over oxidative phosphorylation (OXPHOS). However, there is emerging evidence that (a) dysfunctional OXPHOS may be a major factor driving oncogene addiction and (b) feedback activation of the transcription factor STAT3 is a common surrogate survival pathway in oncogene addicted cancer cells. As such, invasive cancers exhibit enhanced oxidative phosphorylation, mitochondrial biogenesis and mitochondrial oxygen consumption rate. Therefore, inhibiting OXPHOS and STAT3 activity could have potential therapeutic implications for oncogene addicted and OXPHOS-dependent cancers. Here we report that oncogene addicted non-small cell lung carcinoma (NSCLC) cell line HCC827 and its gefitinib resistant clone and malignant melanoma cell line A375 and its vemurafanib resistant clone have significantly higher OXPHOS activity. In addition, these cells express higher level of the mitochondrial electron transport chain complex I protein (NDUFA9) and increased complex I activity as well as higher mitochondrial DNA copy number. Of note, significantly increased activity of STAT3 is detected in oncogene addicted cancer cells, and the increased mitochondrial oxygen consumption and complex I activity could be significantly inhibited by a novel small molecule inhibitor of STAT3, OPB-51602. The latter is shown to be an effect that might be independent of the STAT3 inhibitory activity of the small molecule compound. Most importantly, the novel STAT3 inhibitor showed strong activity in three different murine models of carcinogenesis as well as in patients treated with the STAT3 inhibitor. These data provide evidence that oncogene addicted cancer cells switch to OXPHOS over glycolysis and serve as proof of principle for identifying targeted new OXPHOS inhibitor in recalcitrant cancers. Citation Format: Jayshree L. Hirpara, Jie Eu Qing, Andrea Wong, Naoto Ohi, Tsunoda Takeshi, Boon Cher Goh, Shazib Pervaiz. OXPHOS: A novel target for cancer therapy in oncogene addicted tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4884.
Optimization of Nb2O5/Ag/Nb2O5 multilayers as transparent composite electrode on flexible substrate with high figure of merit (2012)

Different multilayer structures of Nb2O5/Ag/Nb2O5 have been deposited onto flexible substrates by sputtering at room temperature to develop an indium free transparent composite electrode. The effect of Ag thickness on the electrical and optical properties of the multilayer stack has been studied in accordance with the Ag morphology. The critical thickness of Ag to form a continuous conducting layer is found to be 9.5 nm. A new conduction mechanism has been proposed to describe the conduction before and after the critical thickness. The effective Hall resistivity of the optimized films is as low as 6.44 × 10−5 Ω-cm with a carrier concentration and mobility of 7.4 × 1021 cm−3 and 13.1 cm2 /V-s, respectively, at the critical Ag layer thickness. The multilayer stack has been optimized to obtain a sheet resistance of 7.2 Ω/sq and an average optical transmittance of 86% at 550 nm without any substrate heating or post-annealing process. The Haacke figure of merit (FOM) has been calculated for the films, and the multilayer with a 9.5 nm thick Ag layer has the highest FOM at 31.5 × 10-3 Ω−1, which is one of the highest FOM values reported for TCE deposited at room temperature on a flexible substrate.
Assessment of Intrapartum Antibiotic Prophylaxis for the Prevention of Early-onset Group B Streptococcal Disease (2011)

IAP was effective in interrupting mother-to-newborn transmission of GBS. However, approximately 10% of prenatally GBS-negative women were positive during labor and missed IAP, whereas approximately 50% of prenatally GBS-positive women were negative during labor and received IAP. These findings emphasize the need for rapid diagnostics during labor.
The State of Charge Estimation of Lithium-Ion Batteries Based on a Proportional-Integral Observer (2013)

With the development of electric drive vehicles (EDVs), the state-of-charge (SOC) estimation for lithium-ion (Li-ion) batteries has become increasingly more important. Based on the analysis of some of the most popular model-based SOC estimation methods, the proportional-integral (PI) observer is proposed to estimate the SOC of lithium-ion batteries in EDVs. The structure of the proposed PI observer is analyzed, and the convergence of the estimation method with model errors is verified. To demonstrate the superiority and compensation properties of the proposed PI observer, the simple-structure RC battery model is utilized to model the Li-ion battery. To validate the results of the proposed PI-based SOC estimation method, the experimental battery test bench is established. In the validation, the urban dynamometer driving schedule (UDDS) drive cycle is utilized, and the PI-based SOC estimation results are found to agree with the reference SOC, generally within the 2% error band for both the known and unknown initial SOC cases.
Upper Bounds on the Error of Sparse Vector and Low-Rank Matrix Recovery (2015)

Suppose that a solution $\widetilde{\mathbf{x}}$ to an underdetermined linear system $\mathbf{b} = \mathbf{A} \mathbf{x}$ is given. $\widetilde{\mathbf{x}}$ is approximately sparse meaning that it has a few large components compared to other small entries. However, the total number of nonzero components of $\widetilde{\mathbf{x}}$ is large enough to violate any condition for the uniqueness of the sparsest solution. On the other hand, if only the dominant components are considered, then it will satisfy the uniqueness conditions. One intuitively expects that $\widetilde{\mathbf{x}}$ should not be far from the true sparse solution $\mathbf{x}_0$. We show that this intuition is the case by providing an upper bound on $\| \widetilde{\mathbf{x}} - \mathbf{x}_0\|$ which is a function of the magnitudes of small components of $\widetilde{\mathbf{x}}$ but independent from $\mathbf{x}_0$. This result is extended to the case that $\mathbf{b}$ is perturbed by noise. Additionally, we generalize the upper bounds to the low-rank matrix recovery problem.
Decentralized control of sound radiation from an aircraft-style panel using iterative loop recovery (2008)

A decentralized LQG-based control strategy is designed to reduce low-frequency sound transmission through periodically stiffened panels. While modern control strategies have been used to reduce sound radiation from relatively simple structural acoustic systems, significant implementation issues have to be addressed before these control strategies can be extended to large systems such as the fuselage of an aircraft. For instance, centralized approaches typically require a high level of connectivity and are computationally intensive, while decentralized strategies face stability problems caused by the unmodeled interaction between neighboring control units. Since accurate uncertainty bounds are not known a priori, it is difficult to ensure the decentralized control system will be robust without making the controller overly conservative. Therefore, an iterative approach is suggested, which utilizes frequency-shaped loop recovery. The approach accounts for modeling error introduced by neighboring control loops, requires no communication between subsystems, and is relatively simple. The control strategy is validated using real-time control experiments performed on a built-up aluminum test structure representative of the fuselage of an aircraft. Experiments demonstrate that the iterative approach is capable of achieving 12 dB peak reductions and a 3.6 dB integrated reduction in radiated sound power from the stiffened panel.
Applications of Synthetic Peptides (2002)

Abstract For Abstract see ChemInform Abstract in Full Text.
Structure–activity correlation in aerobic cyclohexene oxidation and peroxide decomposition over CoxFe3−xO4 spinel oxides (2022)

Aerobic cyclohexene oxidation and peroxide decomposition in the liquid phase were performed over a series of Co x Fe 3− x O 4 spinel catalysts exhibiting a volcano plot for the catalytic activity with a maximum at x = 1.
Wavelet domain ML reconstruction in positive emission tomography (2002)

A classic technique for reconstruction of Positive Emission Tomography (PET) images from measured projections is based on the maximum likelihood (ML) parameter estimation along with the Expectation Maximization (EM) algorithm. The authors incorporate the Wavelet transform (WT) into the ML framework, and obtain a new iterative algorithm that incorporates local and multiresolution properties of the WT within the structure of the EM. Using the WT allows one to embed regularization procedures (filtering) into the iterative process, by imposing a new set of parameters on a subset of wavelet coefficients with a desired resolution. Properties of the proposed algorithm are demonstrated on reconstructions of a synthetic brain phantom.
MR1-Restricted MAIT Cells From The Human Lung Mucosal Surface Have Distinct Phenotypic, Functional, and Transcriptomic Features That Are Preserved in HIV Infection (2021)

Mucosal associated invariant T (MAIT) cells are a class of innate-like T cells that utilize a semi-invariant αβ T cell receptor to recognize small molecule ligands produced by bacteria and fungi. Despite growing evidence that immune cells at mucosal surfaces are often phenotypically and functionally distinct from those in the peripheral circulation, knowledge about the characteristics of MAIT cells at the lung mucosal surface, the site of exposure to respiratory pathogens, is limited. HIV infection has been shown to have a profound effect on the number and function of MAIT cells in the peripheral blood, but its effect on lung mucosal MAIT cells is unknown. We examined the phenotypic, functional, and transcriptomic features of major histocompatibility complex (MHC) class I-related (MR1)-restricted MAIT cells from the peripheral blood and bronchoalveolar compartments of otherwise healthy individuals with latent <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) infection who were either HIV uninfected or HIV infected. Peripheral blood MAIT cells consistently co-expressed typical MAIT cell surface markers CD161 and CD26 in HIV-negative individuals, while paired bronchoalveolar MAIT cells displayed heterogenous expression of these markers. Bronchoalveolar MAIT cells produced lower levels of pro-inflammatory cytokine IFN-γ and expressed higher levels of co-inhibitory markers PD-1 and TIM-3 than peripheral MAIT cells. HIV infection resulted in decreased frequencies and pro-inflammatory function of peripheral blood MAIT cells, while in the bronchoalveolar compartment MAIT cell frequency was decreased but phenotype and function were not significantly altered. Single-cell transcriptomic analysis demonstrated greater heterogeneity among bronchoalveolar compared to peripheral blood MAIT cells and suggested a distinct subset in the bronchoalveolar compartment. The transcriptional features of this bronchoalveolar subset were associated with MAIT cell tissue repair functions. In summary, we found previously undescribed phenotypic and transcriptional heterogeneity of bronchoalveolar MAIT cells in HIV-negative people. In HIV infection, we found numeric depletion of MAIT cells in both anatomical compartments but preservation of the novel phenotypic and transcriptional features of bronchoalveolar MAIT cells.
Protection against VirulentMycobacterium aviumInfection following DNA Vaccination with the 35-Kilodalton Antigen Is Accompanied by Induction of Gamma Interferon-Secreting CD4+T Cells (2000)

Mycobacterium avium is an opportunistic pathogen that primarily infects immunocompromised individuals, although the frequency of M. avium infection is also increasing in the immunocompetent population. The antigen repertoire of M. avium varies from that of Mycobacterium tuberculosis, with the immunodominant 35-kDa protein being present in M. avium and Mycobacterium leprae but not in members of the M. tuberculosis complex. Here we show that a DNA vector encoding this M. avium 35-kDa antigen (DNA-35) induces protective immunity against virulent M. avium infection, and this protective effect persists over 14 weeks of infection. In C57BL/6 mice, DNA vaccines expressing the 35-kDa protein as a cytoplasmic or secreted protein, both induced strong T-cell gamma interferon (IFN-gamma) and humoral immune responses. Furthermore, the antibody response was to conformational determinants, confirming that the vector-encoded protein had adopted the native conformation. DNA-35 immunization resulted in an increased activated/memory CD4(+) T-cell response, with an accumulation of CD4(+) CD44(hi) CD45RB(lo) T cells and an increase in antigen-specific IFN-gamma production. The protective effect of the DNA-35 vectors against M. avium infection was comparable to that of vaccination with Mycobacterium bovis BCG and significantly greater than that for previous treated infection with M. avium. These results illustrate the importance of the 35-kDa protein in the protective response to M. avium infection and indicate that DNA vaccination successfully promotes a sustained level of protection during chronic M. avium infection.
The Management of Extensor Mechanism Complications in Total Knee Arthroplasty (2014)

Complications involving the knee extensor mechanism and patellofemoral joint occur in 1% to 12% of patients following total knee arthroplasty and have major negative effects on patient outcomes and satisfaction. The surgeon must be aware of intraoperative, postoperative, and patient-related factors that can increase the rate of these problems. This review focuses on six of the most commonly encountered problems: patellar tendon disruption, quadriceps tendon rupture, patellar crepitus and soft-tissue impingement, periprosthetic patellar fracture, patellofemoral instability, and osteonecrosis of the patella. The goals of this report are to (1) review the relevant anatomy of the knee extensor mechanism, (2) present risk factors that may lead to extensor mechanism complications, (3) provide a diagnostic and treatment algorithm for each of the aforementioned problems, and (4) review the specific surgical techniques of Achilles tendon allograft reconstruction and synthetic mesh augmentation. Extensor mechanism disorders following total knee arthroplasty remain difficult to manage effectively. Although various surgical techniques have been used, the results in patients with a prior total knee arthroplasty are inferior to the results in the young adult without such a prior procedure. Surgical attempts at restoration of the knee extensor mechanism are usually warranted; however, the outcomes of treatment of these complications are often poor, and management of patient expectations is important.
All‐Organic Vapor Sensor Using Inkjet‐Printed Reduced Graphene Oxide (2010)

Flexibler Sensor: Filme aus Graphenoxid und reduziertem Graphenoxid wurden mithilfe der Tintenstrahltechnik auf eine flexible Kunststoffoberfläche gedruckt (siehe Bild) und zum Nachweis aggressiver Gase wie NO2 und Cl2 genutzt. Ohne Aufkonzentrieren können die Gase in Luftproben im Konzentrationsbereich 100 ppm–500 ppb nachgewiesen werden.
Lidar metrology for prescription characterization and alignment of large mirrors (2011)

We describe the use of LIDAR, or "laser radar," (LR) as a fast, accurate, and non-contact tool for the measurement of the radius of curvature (RoC) of large mirrors. We report the results of a demonstration of this concept using a commercial laser radar system. We measured the RoC of a 1.4m x 1m spherical mirror with a nominal RoC of 4.6m with a manufacturing tolerance of 4600mm +/- 6mm. The prescription of the mirror is related to its role as ground support equipment used in the test of part of the James Webb Space Telescope (JWST). The RoC of such a large mirror is not easily measured without contacting the surface. From a position near the center of curvature of the mirror, the LIDAR scanned the mirror surface, sampling it with 1 point per 3.5 cm<sup>2</sup>. The measurement consisted of 3983 points and lasted only a few minutes. The laser radar uses the LIDAR signal to provide range, and encoder information from angular azimuth and elevation rotation stages provide the spherical coordinates of a given point. A best-fit to a sphere of the measured points was performed. The resulting RoC was within 20 ppm of the nominal RoC, also showing good agreement with the results of a laser tracker-based, contact metrology. This paper also discusses parameters such as test alignment, scan density, and optical surface type, as well as future possible application for full prescription characterization of aspherical mirrors, including radius, conic, off-axis distance, and aperture.