gebhart/patrepeval huggingface dataset:
Extracellular Cyclophilin A Augments Platelet-Dependent Thrombosis and Thromboinflammation (2017)

Cyclophilin A (CyPA) is involved in the pathophysiology of several inflammatory and cardiovascular diseases. To our knowledge, there is no specific inhibitor targeting extracellular CyPA without affecting other extracellular cyclophilins or intracellular CyPA functions. In this study, we developed an antibody-based inhibitor of extracellular CyPA and analysed its effects <i>in vitro</i> and <i>in vivo</i>. To generate a specific antibody, mice and rats were immunized with a peptide containing the extracellular matrix metalloproteinase inducer binding site and various antibody clones were selected and purified. At first, antibodies were tested for their binding capacity to recombinant CyPA and their functional activity. The clone 8H7-mAb was chosen for further experiments. 8H7-mAb reduced the CyPA-induced migration of inflammatory cells <i>in vitro</i> and <i>in vivo</i>. Furthermore, 8H7-mAb revealed strong antithrombotic effects by inhibiting CyPA-dependent activation of platelets and thrombus formation <i>in vitro</i> and <i>in vivo</i>. Surprisingly, 8H7-mAb did not influence <i>in vivo</i> tail bleeding time or <i>in vitro</i> whole blood coagulation parameters. Our study provides first evidence that antibody-based inhibition of extracellular CyPA inhibits thrombosis and thromboinflammation without affecting blood homeostasis. Thus, 8H7-mAb may be a promising compound for thrombi modulation in inflammatory diseases to prevent organ dysfunction.
Coverage expansion with cooperation (2008)

For practical implementation of cooperative communications in wireless networks, we need to develop protocols by which nodes are assigned to cooperate with each other. In most of the previous chapters on cooperation, the cooperating relays are assumed to exist and are already paired with the source nodes in the network. A deterministic network topology, i.e., deterministic channel gain variances between different nodes in the network, was also assumed. If the random users' spatial distribution, and the associated propagation path losses between different nodes in the network, are taken into consideration, then these assumptions, in general, are no longer valid.
Cricothyrotomy Simulator with Computational Skill Assessment for Procedural Skill Training in the Developing World (2013)

Objectives: Cricothyrotomy is a life‐saving procedure performed when an airway cannot be established through less invasive techniques. The goals of this study were to 1) design and build a low‐cost simulator that teaches essential anatomy, and 2) provide a method of data collection for performance evaluation and guided instruction. Methods: The design of the simulator was optimized for materials that are low‐cost and widely available and for accurate anatomical landmarks. It was designed to electronically record instrument contact with critical anatomical locations throughout the procedure. Three simulators were constructed, and data were collected during 20 procedures performed by participants of varying surgical experience level. Surveys were completed by all participants to assess the perceived quality of the simulator. Three experts graded the recorded procedures by completing an Objective Structured Assessment of Technical Skills (OSATS) survey. Results: A simulator was designed and built. Procedural data of 20 subjects were collected. The survey data showed the majority of participants answered “moderate” or “very” on questions related to 1) anatomical accuracy (85%), 2) realism (50%), 3) improved understanding of procedure (65%), and 4) useful for practice (85%). The OSATS data correlated with task time. Conclusions: A cricothyrotomy simulator for use in a low‐resource environment was designed and produced. It collects data that can be used for performance evaluation and instruction. These were analyzed against OSATS data. A study of 20 subjects, 12 of whom were experts, demonstrated that it was realistic, anatomically accurate, and useful for practice and improving procedure knowledge.
CACHE (Critical Assessment of Computational Hit-finding Experiments): A public–private partnership benchmarking initiative to enable the development of computational methods for hit-finding (2022)

One aspirational goal of computational chemistry is to predict potent and drug-like binders for any protein, such that only those that bind are synthesized. In this Roadmap, we describe the launch of Critical Assessment of Computational Hit-finding Experiments (CACHE), a public benchmarking project to compare and improve small molecule hit-finding algorithms through cycles of prediction and experimental testing. Participants will predict small molecule binders for new and biologically relevant protein targets representing different prediction scenarios. Predicted compounds will be tested rigorously in an experimental hub, and all predicted binders as well as all experimental screening data, including the chemical structures of experimentally tested compounds, will be made publicly available, and not subject to any intellectual property restrictions. The ability of a range of computational approaches to find novel binders will be evaluated, compared, and openly published. CACHE will launch 3 new benchmarking exercises every year. The outcomes will be better prediction methods, new small molecule binders for target proteins of importance for fundamental biology or drug discovery, and a major technological step towards achieving the goal of Target 2035, a global initiative to identify pharmacological probes for all human proteins.
AMP-Activated Protein Kinase Mediates the Effect of Leptin on Avian Autophagy in a Tissue-Specific Manner (2018)

Autophagy, a highly conserved intracellular self-digestion process, plays an integral role in maintaining cellular homeostasis. Although emerging evidence indicate that the endocrine system regulates autophagy in mammals, there is still a scarcity of information on autophagy in avian (non-mammalian) species. Here, we show that intracerebroventricular administration of leptin reduces feed intake, modulates the expression of feeding-related hypothalamic neuropeptides, activates leptin receptor and signal transducer and activator of transcription (Ob-Rb/STAT) pathway, and significantly increases the expression of autophagy-related proteins (Atg3, Atg5, Atg7, beclin1, and LC3B) in chicken hypothalamus, liver, and muscle. Similarly, leptin treatment activates Ob-Rb/STAT pathway and increased the expression of autophagy-related markers in chicken hypothalamic organotypic cultures, muscle (QM7) and hepatocyte (Sim-CEL) cell cultures as well as in Chinese Hamster Ovary (CHO-K1) cells-overexpressing chicken Ob-Rb and STAT3. To define the downstream mediator(s) of leptin's effects on autophagy, we determined the role of the master energy sensor AMP-activated protein kinase (AMPK). Leptin treatment significantly increased the phosphorylated levels of AMPKα1/2 at Thr172 site in chicken hypothalamus and liver, but not in muscle. Likewise, AMPKα1/2 was activated by leptin in chicken hypothalamic organotypic culture and Sim-CEL, but not in QM7 cells. Blocking AMPK activity by compound C reverses the autophagy-inducing effect of leptin. Together, these findings indicate that AMPK mediates the effect of leptin on chicken autophagy in a tissue-specific manner.
Long-Term Oncological Outcomes of Laparoscopic Liver Resection for Solitary Hepatocellular Carcinoma: Comparison of Anatomical and Nonanatomical Resection Using Propensity Score Matching Analysis (2019)

<b><i>Aim:</i></b> There is no evidence indicating that survival improvement is associated with anatomical laparoscopic liver resection (ALLR) rather than non-ALLR (NALLR) to treat solitary hepatocellular carcinoma (HCC). The aim of our study was to compare the oncological outcomes of ALLR versus NALLR. <b><i>Materials and Methods:</i></b> From January 2008 to September 2014, 231 patients underwent LLR as the primary treatment for solitary HCC without portal vein tumor thrombus. After matching one-to-one propensity scores, 118 patients were included in 2 groups: NALLR (<i>n</i> = 59) and ALLR (<i>n</i> = 59). <b><i>Results:</i></b> In the propensity-matched cohort, the 1-, 3-, and 5-year recurrence-free survival rates were 84.4%, 73.8%, and 68.4% in the ALLR group and 87.7%, 78.7%, and 73.5% in the NALLR group (<i>P</i> = .602). In multivariate analysis, the independent risk factors affecting HCC recurrence were higher preoperative PIVKA-II (prothrombin induced by vitamin K absence or antagonist-II) levels (<i>P</i> = .041) and microvascular invasion (<i>P</i> = .030). The risk factor affecting liver-related mortality was determined to be higher preoperative PIVKA-II levels (<i>P</i> = .007). <b><i>Conclusions:</i></b> In the propensity-matched cohort, long-term outcomes of the NALLR group were not inferior to those of the ALLR group.
Abstract 15004: Real Time Lesion Assessment Using a Novel Combined Polarization-Sensitive Optical Coherence Reflectometry (2016)

Introduction: Real-time lesion assessment could improve ablation efficiency and safety by allowing energy titration for transmurality. Incorporating polarization sensitive OCT (PS-OCT) within a cus...
Colorectal cancer chemoprevention: the potential of a selective approach (2010)

Colorectal cancer (CRC) is a leading cause of cancer death, and therefore demands special attention. Novel recent approaches for the chemoprevention of CRC focus on selective targeting of key pathways. We review the study by Zhang and colleagues, evaluating a selective approach targeting APC-deficient premalignant cells using retinoid-based therapy and TNF-related apoptosis-inducing ligand (TRAIL). This study demonstrates that induction of TRAIL-mediated death signaling contributes to the chemopreventive value of all-trans-retinyl acetate (RAc) by sensitizing premalignant adenoma cells for apoptosis without affecting normal cells. We discuss these important findings, raise few points that deserve consideration, and may further contribute to the development of RAc-based combination therapies with improved efficacy. The authors clearly demonstrate a synergistic interaction between TRAIL, RAc and APC, which leads to the specific cell death of premalignant target cells. The study adds to the growing body of literature related to CRC chemoprevention, and provides solid data supporting a potentially selective approach for preventing CRC using RAc and TRAIL.
A phase I trial of weekly combination KOS-862 (Epothilone D) and trastuzumab in HER-2 overexpressing malignancies (2006)

2028 Background: KOS-862 (Epothilone D) (K) has shown single agent activity against metastatic breast cancer (MBC) and NSCLC. Trastuzumab (H) is standard therapy for HER-2 overexpressing MBC. This phase IB trial determined the safety and PK profile of KOS-862 in a weekly schedule with H. Methods: Eligibility: pts with HER-2 overexpressing (IHC 3+ or FISH +) chemo-refractory tumors, ECOG ≤ 2, neuropathy ≤ gr 1, no CNS metastases, and no H ≤ 6 mo. prestudy. H given as a 4 mg/kg loading dose, then 2 mg/kg wkly. K given as a 90 min iv infusion wkly × 3 Q 4 wks after H. K dose escalation cohorts: 70, 85 &amp; 100 mg/m 2 . H1 + H2 antagonists + corticosteroid prophylaxis given 30–60 min prior to K. DLT: gr 4 hematologic or gr 3 other toxicity, or toxicity requiring &gt;4 wk treatment delay. Cycle 1 + 2 PK samples obtained for K + H. Results: 13 pts treated from 9/04 - 8/05. Median age 51 yrs (36–65). All pts had MBC. Prior H therapy n = 9, prior taxane n = 11. Enrollment: 70 mg/m 2 (4), 85 mg/m 2 (3), and 100 mg/m 2 (6). Mean number cycles 3.9 (1–6). The 100 mg/m 2 cohort was expanded to 6 pts per study design; no DLTs were noted. Toxicity: Principal neurotoxicities (gr 3 noted, if present): parasthesias (10 pts, 1 gr3), neuropathic pain (5 pts, 2 gr3), dizziness (4 pts), dysguesia (4 pts), ataxia (3 pts), transient confusion (3 pts), dysesthesias (2 pts), insomnia (2 pts). No gr 4 neurotoxicities reported. Non-neurologic toxicities were limited to gr 1/2 and included diarrhea, pyrexia, abdominal and back pain, arthralgias. PK (n = 13): KOS-862 CL 21 ± 10 L/hr, V z 260 ± 110 L, T 1/2 9.8 ± 3.9 hr. Seco-metabolite was 67% ± 35% of K. At 100 mg/m 2 K dose (n = 6): C max 3.3 ± 1.1 μg/mL and AUC inf 11.0 ± 7.5 h*(g/mL). Neither K nor its seco-metabolite PK were affected by H. Responses: An 85 mg/m 2 K pt (no prior H or taxane) had confirmed PR and a 100 mg/m 2 K pt (prior taxane) had an unconfirmed PR. A 2 nd 100 mg/m 2 pt (no prior H or taxane, bone only disease) had &gt; 90% CEA reduction. Conclusions: This phase I study demonstrates feasibility of full dose wkly KOS-862 coadministration with wkly H. Treatment-related toxicities were all gr 1 / 2, except for 3 cases gr 3 paresthesias and neuropathic pain. PK of K and its principal metabolite were not affected by H. Three clinical responses were observed; a phase II trial of this combination is ongoing in minimally-pretreated MBC. [Table: see text]
Supersonic metal cluster beams: laser photoionization studies of copper cluster (Cu2) (1982)

Laser vaporization of a rotating metal target within a pulsed supersonic nozzle has been used to produce ultracold beams of copper clusters. Photoionization with an argon fluoride excimer laser followed by time-of-flight mass spectrometric analysis showed the cold beam to contain clusters in the range from 1 through 13 copper atoms. The ionization potential (IP) of the small clusters was seen to alternate above and below the 6.4-eV laser photon energy depending upon whether the cluster contained an even (high IP) or odd (low IP) number of copper atoms. The absorption spectrum of Cu2 was recorded in the 4480-4660-Å region by using two-color resonant two-photon ionization. The Cu2 cluster beam was found to have translational, rotational, and vibrational temperatures of <5, <10, and 50-100 K, respectively. In addition to the known B 1Σu+ ← X 1Σg+ band system, a new system was found in the same spectral range. Parameters for the new system were Te = 21867 ± 4 cm-1, ωe′ = 226 ± 3 cm-1, ωeXe′ = 3 ± 2 cm-1. The lifetime of the B state was found to be 35 ± 10 ns for the vibrational levels υ′ = 0 and 1, and it is argued this short lifetime is likely due to predissociation. The lifetime of the new C state was found to be 1.0 ± 0.2 μs. © 1982 American Chemical Society.
Close Association Between Platelet Biogenesis and Alveolarization of the Developing Lung (2021)

Bronchopulmonary dysplasia (BPD) is a neonatal chronic lung disease characterized by an arrest in alveolar and vascular development. BPD is secondary to lung immaturity, ventilator-induced lung injury, and exposure to hyperoxia in extremely premature infants, leading to a lifelong impairment of lung function. Recent studies indicate that the lung plays an important role in platelet biogenesis. However, the dynamic change of platelet production during lung development and BPD pathogenesis remains to be elucidated. We investigated the dynamic change of platelet parameters in extremely premature infants during BPD development, and in newborn rats during their normal development from birth to adulthood. We further studied the effect of hyperoxia exposure on platelet production and concomitant pulmonary maldevelopment in an experimental BPD rat model induced by prolonged exposure to hyperoxia. We detected a physiological increase in platelet count from birth to 36 weeks postmenstrual age in extremely premature infants, but platelet counts in extremely premature infants who developed BPD were persistently lower than gestational age-matched controls. In line with clinical findings, exposure to hyperoxia significantly decreased the platelet count in neonatal rats. Lung morphometry analysis demonstrated that platelet counts stabilized with the completion of lung alveolarization in rats. Our findings indicate a close association between platelet biogenesis and alveolarization in the developing lung. This phenomenon might explain the reduced platelet count in extremely premature infants with BPD.
Productive Infection of Primary Macrophages with Human Herpesvirus 7 (2001)

Here we demonstrate replication of human herpesvirus 7 (HHV-7), a T-lymphotropic virus, in macrophages. Productive replication was lost after 2 weeks, but HHV-7 DNA was detected up to 1 month after infection. Thus, macrophages become infected by HHV-7 and might play an important role as a viral reservoir, as has been demonstrated for human immunodeficiency virus type 1.
ChemInform Abstract: XPS and EXAFS Studies of the Reactions of Co(III) Ammine Complexes with GaAs Surfaces. (1990)

Abstract The chemisorption of Co(II) and Co(III) complexes onto GaAs surfaces is investigated by a combination of XPS, X‐ray absorption spectroscopy, and radiotracer techniques.
Dielectric resonator antenna with orthogonal slotline feed (2004)

International audience
Through the Lens of a Large Instant-Messaging Network: Planetary-Scale Views on Behavior (2009)

Behavioral Studies at Planetary Scale Research questions: What are key structural properties of the communication graph? How do geographic relationships affect communication? How are communication patterns influenced by demographics (age, sex, language, country)?
Antigenic peptide interaction with MHC molecules: implications for the design of artificial vaccines. (1991)

Both helper and cytotoxic T cells see primarily a limited number of immunodominant sites on a protein. The reasons for immunodominance are many. We have explored primarily the roles of antigen processing and binding to histocompatibility molecules, as well as the structural features of the antigenic peptide. This information has led to the identification and characterization of sites stimulating helper or cytotoxic T cells specific for antigens from malaria or HIV, and ways to couple and immunize with these, that may be useful for vaccine development. We also observed a striking concordance between helper and cytotoxic T cell sites.
Kinetic and mechanistic aspects of the NO oxidation by O2 in aqueous phase (1994)

Abstract The oxidation kinetics of NO by O 2 in aqueous solution was observed using a stopped flow apparatus. The kinetics follows a third order rate law of the form k · [NO] 2 · [O 2 ] in analogy to gas‐phase results. The rate constant at 296 K was measured as (6.4 ± 0.8) · 10 6 M −2 s −1 with an activation energy of 2.3 kcal/mol and a preexponential factor of (4.0 ± 0.5) · 10 8 M −2 s −1 . The rate constant displays a very slight pH dependence corresponding to less than a factor of three over the range 0 to 12. The system NO/O 2 in aqueous solution is an efficient nitrosating agent which has been tested using phenol as a substrate over the pH range 0 to 12. The rate limiting step leading to formation of 4‐nitrosophenol is the formation of the reactive intermediate whose competitive hydrolysis yields HONO or NO 2 − . The absence of NO 3 − in the autoxidation of NO, the exclusive presence of NO 2 − as a product of the nitrosation reaction of phenol, and the kinetic results of the N 3 − trapping experiments point towards N 2 O 3 as the reactive intermediate. © 1994 John Wiley &amp; Sons, Inc.
Technical considerations in the use of "high-performance" liquid chromatography in therapeutic drug monitoring. (1983)

I review the methodology of "high-performance" liquid chromatography as applied to therapeutic drug monitoring. Aside from direct injection of sample, sample cleanup involves miscible and immiscible organic solvent extractions, solid-phase extraction, and size separations. Column considerations are bonded phases, column dimensions, particle size, guard columns, stability, pH range, and reproducibility. In a section on mobile phase, the reversed-phase mode is discussed along with temperature and degassing. Absorbance and fluorescence detectors are used most commonly. The parameters "capacity factor," "efficiency," and "asymmetry value" are helpful for interpreting chromatograms, as are the aspects of peak tailing, peak quantitation, "complex solutes," and "crowded chromatograms." Finally, automation, competing methodology, and prospects are discussed.
A simple synthesis of (+)- and (−)-alkaloid 241D and C-4 epimers (2000)

An enantioselective preparation of both enantiomers of alkaloid 241D 1 and its C-4 epimer is reported. This simple and concise synthesis, seven steps from pent-3-en-2-one, involves a highly diastereoselective Mannich-type cyclisation as the key step.
Recent advances in inertial-electrostatic confinement (IEC) fusion for space power and propulsion (2000)

Concept Studies have shown the IEC to be one of the most attractive approaches to fusion propulsion, provided the physics and technology involved can be scaled-up to high power levels. A key step involves development of a pulsed IEC that can obtain high ion currents along with good ion confinement. Results from initial pulsed IEC experiments are described here. The obtainment of a D-D fusion neutron yield of 8×108 n/s at a peak pulse current of 17 A demonstrates that the dynamic formation of the required accelerating fields with the IEC discharge is possible. A next step involves improvement in confinement.
Visual Prediction of Rover Slip: Learning Algorithms and Field Experiments (2008)

Perception of the surrounding environment is an essential tool for intelligent navigation in any autonomous vehicle. In the context of Mars exploration, there is a strong motivation to enhance the perception of the rovers beyond geometry-based obstacle avoidance, so as to be able to predict potential interactions with the terrain. In this thesis we propose to remotely predict the amount of slip, which reflects the mobility of the vehicle on future terrain. The method is based on learning from experience and uses visual information from stereo imagery as input. We test the algorithm on several robot platforms and in different terrains. We also demonstrate its usefulness in an integrated system, onboard a Mars prototype rover in the JPL Mars Yard. Another desirable capability for an autonomous robot is to be able to learn about its interactions with the environment in a fully automatic fashion. We propose an algorithm which uses the robot's sensors as supervision for vision-based learning of different terrain types. This algorithm can work with noisy and ambiguous signals provided from onboard sensors. To be able to cope with rich, high-dimensional visual representations we propose a novel, nonlinear dimensionality reduction technique which exploits automatic supervision. The method is the first to consider supervised nonlinear dimensionality reduction in a probabilistic framework using supervision which can be noisy or ambiguous. Finally, we consider the problem of learning to recognize different terrains, which addresses the time constraints of an onboard autonomous system. We propose a method which automatically learns a variable-length feature representation depending on the complexity of the classification task. The proposed approach achieves a good trade-off between decrease in computational time and recognition performance.