gebhart/patrepeval huggingface dataset:
Aromatic Oligoamides with a Rare ortho‐Connectivity: Synthesis and Study of ortho‐Arylopeptoids (2013)

Abstract Even though aromatic oligoamides composed of aromatic amino acids in a “one‐way sequence” attract ever increasing research interest, backbones connected through ortho ‐linked aromatics remain rare. Herein, we present the first synthesis and study of N ‐alkylated ortho ‐aminomethyl‐benzamides termed “ ortho ‐arylopeptoids”. The ortho ‐arylopeptoids may, with a few exceptions, be synthesized either in solution or on solid‐phase using unique and highly efficient submonomer methods with similar levels of high generality and efficiency to those previously demonstrated for meta ‐ and para ‐arylopeptoids. NMR studies indicated a more restricted rotation about the amide bonds in ortho ‐arylopeptoids, presumably due to a more congested backbone structure resulting from the ortho ‐connectivity pattern. Intriguingly, tert ‐butyl and phenyl side chains offer complete control over the amide conformations; whereas arylopeptoid residues with tert ‐butyl side chains adopt a 100 % cis amide conformation, the opposite 100 % trans amide conformation was observed in arylopeptoids with phenyl side chains. The tert ‐butyl moiety can furthermore serve as a protecting group during synthesis, which can later be removed to allow the amide to adopt a 100 % trans conformation instead.
A Live Attenuated Vaccine for Lassa Fever Made by Reassortment of Lassa and Mopeia Viruses (2005)

Lassa virus (LASV) and Mopeia virus (MOPV) are closely related Old World arenaviruses that can exchange genomic segments (reassort) during coinfection. Clone ML29, selected from a library of MOPV/LASV (MOP/LAS) reassortants, encodes the major antigens (nucleocapsid and glycoprotein) of LASV and the RNA polymerase and zinc-binding protein of MOPV. Replication of ML29 was attenuated in guinea pigs and nonhuman primates. In murine adoptive-transfer experiments, as little as 150 PFU of ML29 induced protective cell-mediated immunity. All strain 13 guinea pigs vaccinated with clone ML29 survived at least 70 days after LASV challenge without either disease signs or histological lesions. Rhesus macaques inoculated with clone ML29 developed primary virus-specific T cells capable of secreting gamma interferon in response to homologous MOP/LAS and heterologous MOPV and lymphocytic choriomeningitis virus. Detailed examination of two rhesus macaques infected with this MOPV/LAS reassortant revealed no histological lesions or disease signs. Thus, ML29 is a promising attenuated vaccine candidate for Lassa fever.
Adiabatic two-phase flow frictional pressure drop: Part 1, Critical parameters and friction factors for air-water mixture (1991)

An analysis of air-water frictional pressure drop data for horizontal ducts was made. For small diameter, circular tubes and narrow rectangular channels, it is established that the frictional pressure deep profiles with increasing mixture quality (or superficial gas velocity) are characterized by critical values for gas Reynolds number, quality and friction factor. These characteristic features are in evidence for tests in which the total mass flux of the mixture is held fixed with increasing quality or superficial gas velocity. The effects of duct geometry and total mass flux on the critical parameters are documented and discussed. The results for two-phase flow friction factors are also presented. 18 refs., 7 figs., 1 tab.
An adaptive reservation packet switched multiple access protocol for a wireless network (2002)

This paper addresses the development of an adaptive packet based reservation multiple access protocol to transmit multimedia traffic over a wireless network. The proposed multiple access protocol is an adaptive version of the BRTDMA (block reservation time division multiple access) protocol where resources are allocated based on traffic type in a network. Resources are allocated in such a way that the quality of service parameters of different class of traffic can be maintained. The resource allocation algorithm allocates resources based on QoS requirements of different types of traffic. Simulation results are presented to show the effectiveness of adaptive resource allocation techniques.
Enhancing the Backbone Coplanarity of n-Type Copolymers for Higher Electron Mobility and Stability in Organic Electrochemical Transistors (2022)

Electron-transporting (n-type) conjugated polymers have recently been applied in numerous electrochemical applications, where both ion and electron transport are required. Despite continuous efforts to improve their performance and stability, n-type conjugated polymers with mixed conduction still lag behind their hole-transporting (p-type) counterparts, limiting the functions of electrochemical devices. In this work, we investigate the effect of enhanced backbone coplanarity on the electrochemical activity and mixed ionic-electronic conduction properties of n-type polymers during operation in aqueous media. Through substitution of the widely employed electron-deficient naphthalene diimide (NDI) unit for the core-extended naphthodithiophene diimide (NDTI) units, the resulting polymer shows a more planar backbone with closer packing, leading to an increase in the electron mobility in organic electrochemical transistors (OECTs) by more than two orders of magnitude. The NDTI-based polymer shows a deep-lying lowest unoccupied molecular orbital level, enabling operation of the OECT closer to 0 V vs Ag/AgCl, where fewer parasitic reactions with molecular oxygen occur. Enhancing the backbone coplanarity also leads to a lower affinity toward water uptake during cycling, resulting in improved stability during continuous electrochemical charging and ON-OFF switching relative to the NDI derivative. Furthermore, the NDTI-based polymer also demonstrates near-perfect shelf-life stability over a month-long test, exhibiting a negligible decrease in both the maximum on-current and transconductance. Our results highlight the importance of polymer backbone design for developing stable, high-performing n-type materials with mixed ionic-electronic conduction in aqueous media.
Novel Plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance (2017)

Using this systems biology approach, we identify metabolic shifts that arise with or in support of the resistant phenotype. This perspective allows us to more productively analyze and interpret clinical expression data for the identification of candidate drug targets for the treatment of resistant parasites.
Potential Impact and Effects of Climate Change (2001)

Access A Broad Range of Paleoclimatic Studies. Current debates regarding potential man-induced modification of climate make this volume especially timely. Introductory sections address the major and minor physical controls, or drivers, that affect Earth's climate. Several chapters describe the naturally occurring range of variation of climatic conditions and illustrate past changes in global temperatures. Case studies show how ancient temperature conditions are determined, as well as new techniques that have significant potential as proxies for assessing paleoclimates. Several chapters demonstrate the magnitude and length of duration of numerous temperature variations, which occurred during geologic time periods.
Stimulus response coupling in the human neutrophil. Differential requirements for receptor occupancy in neutrophil responses to a chemoattractant. (1984)

Activated neutrophils aggregate, generate superoxide (O-2), and degranulate. The role of Ca as "second messenger" in neutrophil activation was examined using as agonist the chemotactic peptide fMet-Leu-Phe and its antagonist t-butoxycarbonyl-Phe-Leu-Phe-Leu-Phe to systematically vary the time of receptor occupancy. Release of enzymes from specific and azurophil granules showed a finite requirement for receptor occupancy; the cells were committed to full degranulation after 10 s of receptor-agonist interaction. In contrast, continuous occupation of the receptor by agonist was required to initiate and maintain O-2 generation and aggregation. Cytosolic Ca ( Quin2 fluorescence) increased immediately in response to fMet-Leu-Phe, requiring less than 2 s of agonist-receptor interaction to initiate an optimal response. Mobilization of membrane-associated Ca (chlorotetracycline fluorescence) also demonstrated a finite time requirement; the cells were fully committed after 10 s of agonist-receptor interaction. Increased Ca permeability (45Ca uptake) was fully launched after 15 s of agonist-receptor interaction. The data indicate that Ca movements ( quin2 , chlorotetracycline fluorescence, 45Ca uptake) are both necessary and sufficient to account for degranulation by neutrophils activated by fMet-Leu-Phe. However, neutrophil aggregation and the generation and release of O-2 in response to the same stimulus require a further unknown factor(s) associated with receptor occupancy to maintain these responses.
How hard can it be? Estimating the difficulty of visual search in an image (2017)

We address the problem of estimating image difficulty defined as the human response time for solving a visual search task. We collect human annotations of image difficulty for the PASCAL VOC 2012 data set through a crowd-sourcing platform. We then analyze what human interpretable image properties can have an impact on visual search difficulty, and how accurate are those properties for predicting difficulty. Next, we build a regression model based on deep features learned with state of the art convolutional neural networks and show better results for predicting the ground-truth visual search difficulty scores produced by human annotators. Our model is able to correctly rank about 75% image pairs according to their difficulty score. We also show that our difficulty predictor generalizes well to new classes not seen during training. Finally, we demonstrate that our predicted difficulty scores are useful for weakly supervised object localization (8% improvement) and semi-supervised object classification (1% improvement).
Free Piston Combustion Engine Design Analysis and Challenges (2015)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;There has been a recent resurgence in interest in “free piston” engine designs, particularly for small engine applications. This has been driven primarily by the demand for higher efficiency, flex-fuel capability, and also electrical demand in hybrid-electric applications. In free piston engines, expansion gasses are used to send energy directly to electrical or hydraulic power systems, rather than through a crankshaft. In many instances, the designs use opposed pistons to contribute the momentum of one piston to the upwards stroke of the opposing piston. This paper will review the details and benefits of the early free piston designs and some current designs, including our own hydraulic hybrid engine designs. The paper will then turn to a future free piston engine application that is in development.&lt;/div&gt;&lt;/div&gt;
Vesta Evolution from Surface Mineralogy: Mafic and Ultramafic Mineral Distribution (2014)

Vesta is the only intact, differentiated, rocky protoplanet and it is the parent body of HED meterorites. Howardite, eucrite and diogenite (HED) meteorites represent regolith, basaltic-crust, lower-crust and possibly ultramafic-mantle samples of asteroid Vesta. Only a few of these meteorites, the orthopyroxene-rich diogenites, contain olivine, a mineral that is a major component of the mantles of differentiated bodies, including Vesta. The HED parent body experienced complex igneous processes that are not yet fully understood and olivine and diogenite distribution is a key measurement to understand Vesta evolution. Here we report on the distribution of olivine and its constraints on vestan evolution models.
Discovery and Optimization of HKT288, a Cadherin-6–Targeting ADC for the Treatment of Ovarian and Renal Cancers (2017)

Despite an improving therapeutic landscape, significant challenges remain in treating the majority of patients with advanced ovarian or renal cancer. We identified the cell-cell adhesion molecule cadherin-6 (<i>CDH6</i>) as a lineage gene having significant differential expression in ovarian and kidney cancers. HKT288 is an optimized CDH6-targeting DM4-based antibody-drug conjugate (ADC) developed for the treatment of these diseases. Our study provides mechanistic evidence supporting the importance of linker choice for optimal antitumor activity and highlights CDH6 as an antigen for biotherapeutic development. To more robustly predict patient benefit of targeting CDH6, we incorporate a population-based patient-derived xenograft (PDX) clinical trial (PCT) to capture the heterogeneity of response across an unselected cohort of 30 models-a novel preclinical approach in ADC development. HKT288 induces durable tumor regressions of ovarian and renal cancer models <i>in vivo</i>, including 40% of models on the PCT, and features a preclinical safety profile supportive of progression toward clinical evaluation.<b>Significance:</b> We identify CDH6 as a target for biotherapeutics development and demonstrate how an integrated pharmacology strategy that incorporates mechanistic pharmacodynamics and toxicology studies provides a rich dataset for optimizing the therapeutic format. We highlight how a population-based PDX clinical trial and retrospective biomarker analysis can provide correlates of activity and response to guide initial patient selection for first-in-human trials of HKT288. <i>Cancer Discov; 7(9); 1030-45. ©2017 AACR.</i><i>This article is highlighted in the In This Issue feature, p. 920</i>.
Synthetic and natural factors promoting production of murine and human monoclonal antibodies. (1991)

Human endothelial culture supernatant (HECS) contains factor(s) which promote the growth and the stability of hybridoma cells, and in these respects is superior to the commonly used feeder cells. In particular: HECS increases the recovery of hybridomas after fusion as compared to that in the presence of feeder cells; HECS can substitute feeder cells supporting the growth of hybridomas at the single-cell level under limiting dilution conditions; HECS prolongs the stability of human-mouse hybridomas producing human immunoglobulins (Ig). The active principle which is present in HECS can be different from IL-6. Furthermore the effects of a polyamine derivative, carboxyethyl gamma-aminobutyric acid (CEGABA), were studied on the growth of hybridomas and Epstein-Barr Virus-transformed cell lines. CEGABA enhances the growth of hybridomas through all the steps of hybridoma technology and induces the formation of a large number of EBV-transformed lymphocytes, when added to the culture medium immediately after EBV infection. However, CEGABA shows only a moderate effect on the stability of EBV-transformed cell lines over time, and does not effect the growth of stabilized cell lines. It is possible that CEGABA acts on cells other than EBV-transformed lymphocytes (in fact, after EBV infection all types of mononuclear cells from the blood are present in the culture) and indirectly promotes the growth of EBV-transformed lymphocytes.
Nonnucleoside reverse transcriptase inhibitors are chemical enhancers of dimerization of the HIV type 1 reverse transcriptase (2001)

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are allosteric inhibitors of the HIV type 1 (HIV-1) reverse transcriptase (RT). Yeast grown in the presence of many of these drugs exhibited dramatically increased association of the p66 and p51 subunits of the HIV-1 RT as reported by a yeast two-hybrid assay. The enhancement required drug binding by RT; introduction of a drug-resistance mutation into the p66 construct negated the enhancement effect. The drugs could also induce heterodimerization of dimerization defective mutants. Coimmunoprecipitation of RT subunits from yeast lysates confirmed the induction of heterodimer formation by the drugs. In vitro-binding studies indicate that NNRTIs can bind tightly to p66 but not p51 and then mediate subsequent heterodimerization. This study demonstrates an unexpected effect of NNRTIs on the assembly of RT subunits.
How to Spend Your Robot Time: Bridging Kickstarting and Offline Reinforcement Learning for Vision-based Robotic Manipulation (2022)

Reinforcement learning (RL) has been shown to be effective at learning control from experience. However, RL typically requires a large amount of online interaction with the environment. This limits its applicability to real-world settings, such as in robotics, where such interaction is expensive. In this work we investigate ways to minimize online interactions in a target task, by reusing a suboptimal policy we might have access to, for example from training on related prior tasks, or in simulation. To this end, we develop two RL algorithms that can speed up training by using not only the action distributions of teacher policies, but also data collected by such policies on the task at hand. We conduct a thorough experimental study of how to use suboptimal teachers on a challenging robotic manipulation benchmark on vision-based stacking with diverse objects. We compare our methods to offline, online, offline-to-online, and kickstarting RL algorithms. By doing so, we find that training on data from both the teacher and student, enables the best performance for limited data budgets. We examine how to best allocate a limited data budget -- on the target task -- between the teacher and the student policy, and report experiments using varying budgets, two teachers with different degrees of suboptimality, and five stacking tasks that require a diverse set of behaviors. Our analysis, both in simulation and in the real world, shows that our approach is the best across data budgets, while standard offline RL from teacher rollouts is surprisingly effective when enough data is given.
Inter- and intrasubject variability of the inflammatory response to segmental endotoxin challenge in healthy volunteers (2015)

Segmental endotoxin challenge with lipopolysaccharide (LPS) can be used as a pharmacodynamic model to safely induce a transient airway inflammation in the peripheral lung of healthy subjects and to test the anti-inflammatory efficacy of investigational new drugs. In contrast to whole lung LPS challenge only a fraction of the dose is required that can be precisely administered to a specific lung region and a vehicle challenged segment as an intra-subject control can be included. The aim of this study was to assess the intra- and inter-individual variability of the response to segmental LPS challenge for the appropriate design and power calculation of future clinical trials. Two cohorts with 10 subjects each underwent two segmental LPS challenges within five weeks. The inflammatory response was evaluated in bronchoalveolar lavage (BAL) fluid at 6 (cohort 1) and 24 h (cohort 2) both in the LPS and in a vehicle challenged segment, as well as in plasma for up to 26 h post LPS challenge. While the cytokine response was more pronounced at 6 h, the influx of neutrophils and monocytes dominated at 24 h; e.g. neutrophils increased from a median (inter-quartile range, IQR) of 0.14 (0.16) and 0.09 (0.08)x10(4) cells/mL BAL fluid at baseline to 10.2 (17.1) and 19.3 (15.9)x10(4) cells/mL 24 h after the two separate challenges. The within-subject variability was higher than the between-subject variability for most of the markers. However, sample size estimations based on the variability of outcome variables found lower or equal numbers with cross-over designs compared to parallel group designs for cellular markers at 24 h and cytokine variables at 6 h. The segmental LPS challenge model was safe. Future study designs have to balance between burden to the study subjects (4 versus 2 bronchoscopies), variability (within-versus between-subject), and the desired outcome variable (cells versus chemo/cytokine).
[Preliminary observations on the effect of sjamp on the fibrinolytic system]. (1990)

The effects of Sjamp, an acidic mucopolysaccharide extracted from Stichopus japonicus Selenka, on fibrinolytic activities were studied. The results showed that Sjamp could induce fibrinolysis in vitro, and the effects were stronger than those of heparin. The fibrinolytic activity of Sjamp disappeared when plasminogen was removed from the fibrin clot. This suggested that the fibrinolytic activity of Sjamp might depend upon plasminogen activation. The fibrinolytic activity and FDP concentration of rabbit plasma increased after intravenous injection of Sjamp. Fibrin monomer polymerization (FMP) was also inhibited by Sjamp, so the structure of fibrin clots might be altered, facilitating lysis. The mechanism of fibrinolytic effect of Sjamp and the significance of this effect in biomedicine are discussed.
Dynamic NBTI of p-MOS transistors and its impact on MOSFET scaling (2002)

For the first time, a dynamic negative bias temperature instability (DNBTI) effect in p-MOSFETs with ultrathin gate oxide (1.3 nm) has been studied. The interface traps generated under NBTI stressing corresponding to p-MOSFET operating condition of the "high" output state in a CMOS inverter, are subsequently passivated when the gate to drain voltage switches to positive corresponding to the p-MOSFET operating condition of the "low" output state in the CMOS inverter. Consequently, this DNBTI effect significantly prolongs the lifetime of p-MOSFETs operating in a digital circuit, and the conventional static NBTI (SNBTI) measurement underestimates the p-MOSFET lifetime. A physical model is presented to explain the DNBTI. This finding has significant impact on future scaling of CMOS devices.
Enhanced c-Met activity promotes G-CSF–induced mobilization of hematopoietic progenitor cells via ROS signaling (2010)

Mechanisms governing stress-induced hematopoietic progenitor cell mobilization are not fully deciphered. We report that during granulocyte colony-stimulating factor-induced mobilization c-Met expression and signaling are up-regulated on immature bone marrow progenitors. Interestingly, stromal cell-derived factor 1/CXC chemokine receptor-4 signaling induced hepatocyte growth factor production and c-Met activation. We found that c-Met inhibition reduced mobilization of both immature progenitors and the more primitive Sca-1(+)/c-Kit(+)/Lin(-) cells and interfered with their enhanced chemotactic migration to stromal cell-derived factor 1. c-Met activation resulted in cellular accumulation of reactive oxygen species by mammalian target of rapamycin inhibition of Forkhead Box, subclass O3a. Blockage of mammalian target of rapamycin inhibition or reactive oxygen species signaling impaired c-Met-mediated mobilization. Our data show dynamic c-Met expression and function in the bone marrow and show that enhanced c-Met signaling is crucial to facilitate stress-induced mobilization of progenitor cells as part of host defense and repair mechanisms.
Improving Content-based and Hybrid Music Recommendation using Deep Learning (2014)

Existing content-based music recommendation systems typically employ a \textit{two-stage} approach. They first extract traditional audio content features such as Mel-frequency cepstral coefficients and then predict user preferences. However, these traditional features, originally not created for music recommendation, cannot capture all relevant information in the audio and thus put a cap on recommendation performance. Using a novel model based on deep belief network and probabilistic graphical model, we unify the two stages into an automated process that simultaneously learns features from audio content and makes personalized recommendations. Compared with existing deep learning based models, our model outperforms them in both the warm-start and cold-start stages without relying on collaborative filtering (CF). We then present an efficient hybrid method to seamlessly integrate the automatically learnt features and CF. Our hybrid method not only significantly improves the performance of CF but also outperforms the traditional feature mbased hybrid method.