gebhart/patrepeval huggingface dataset:
Data from Sequence-Specific Pharmacokinetic and Pharmacodynamic Phase I/Ib Study of Olaparib Tablets and Carboplatin in Women's Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Our preclinical studies showed that the PARP inhibitor, olaparib, prior to carboplatin attenuated carboplatin cytotoxicity. We evaluated sequence-specific pharmacokinetic and pharmacodynamic effects, safety, and activity of the combination.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Eligible patients had metastatic or recurrent women's cancer. Olaparib tablets were introduced (100 or 200 mg twice daily, days 1–7) in a 3 + 3 dose escalation with carboplatin AUC4 or 5 every 21 days, up to eight cycles, followed by olaparib 300 mg twice daily maintenance. Patients were randomly assigned to starting schedule: cohort A (olaparib days 1–7, carboplatin on day 8) or B (carboplatin on day 1, olaparib days 2–8) during cycle 1. Patients received the reversed scheme in cycle 2. Blood was collected for olaparib pharmacokinetics, platinum–DNA adducts, comet assay, and PAR concentrations. The primary objectives were to examine schedule-dependent effects on olaparib pharmacokinetics and platinum–DNA adducts.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; A total of 77 (60 ovarian, 14 breast, and 3 uterine cancer) patients were treated. Dose-limiting toxicity was thrombocytopenia and neutropenia, defining olaparib 200 mg twice daily + carboplatin AUC4 as the MTD. Olaparib clearance was increased approximately 50% when carboplatin was given 24 hours before olaparib. &lt;i&gt;In vitro&lt;/i&gt; experiments demonstrated carboplatin preexposure increased olaparib clearance due to intracellular olaparib uptake. Quantities of platinum–DNA adducts were not different as a function of the order of drug administration. Responses included 2 CRs and 31 PRs (46%) with a higher RR in &lt;i&gt;BRCA&lt;/i&gt; mutation carriers compared with nonmutation carriers (68% vs. 19%).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Tablet olaparib with carboplatin is a safe and active combination. Carboplatin preexposure causes intracellular olaparib accumulation reducing bioavailable olaparib, suggesting carboplatin should be administered prior to olaparib. &lt;i&gt;Clin Cancer Res; 23(6); 1397–406. ©2016 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Plant hormones: a key in clubroot development. (2006)

Clubroot disease causes gall formation on Brassica roots. A holistic approach was undertaken to understand the role of plant hormones in early clubroot symptom development in Arabidopsis. We used the CYCB1;1::GUS, DR5::GUS and ARR5::GUS constructs to assess clubroot initiation. We compared plant hormone concentration between control and infected plants, screened different hormone mutants for resistance and evaluated auxin transport. Also, a differential proteome study was performed using two dimensional gel electrophoresis coupled to MALDI-TOF. Combining the hormone and proteome data, we postulate that at the first stages of clubroot disease, cytokinins are produced by the pathogen. This triggers a local re-initiation of cell division in the root cortex. Consequently, a de novo meristematic area is established that acts as a sink for host-derived IAA, carbohydrates, nitrogen and energy to maintain the pathogen and to trigger gall development.
Esophagus Silhouette Extraction and Reconstruction From Fluoroscopic Views for Cardiac Ablation Procedure Guidance (2011)

Cardiac ablation involves the risk of serious complications when thermal injury to the esophagus occurs. This paper proposes to reduce the risk of such injuries by a proactive visualization technique, improving physician awareness of the esophagus location in the absence of or in addition to a reactive monitoring device such as a thermal probe. This is achieved by combining a graphical representation of the esophagus with live fluoroscopy. Toward this goal, we present an automated method to reconstruct and visualize a 3-D esophagus model from fluoroscopy image sequences acquired using different C-arm viewing directions. In order to visualize the esophagus under fluoroscopy, it is first biomarked by swallowing a contrast agent such as barium. Images obtained in this procedure are then used to automatically extract the 2-D esophagus silhouette and reconstruct a 3-D surface of the esophagus internal wall. Once the 3-D representation has been computed, it can be visualized using fluoroscopy overlay techniques. Compared to 3-D esophagus imaging using CT or C-arm CT, our proposed fluoroscopy method requires low radiation dose and enables a simpler workflow on geometry-calibrated standard C-arm systems.
Learning-Based Risk-Averse Model Predictive Control for Adaptive Cruise Control with Stochastic Driver Models (2020)

We propose a learning-based, distributionally robust model predictive control approach towards the design of adaptive cruise control (ACC) systems. We model the preceding vehicle as an autonomous stochastic system, using a hybrid model with continuous dynamics and discrete, Markovian inputs. We estimate the (unknown) transition probabilities of this model empirically using observed mode transitions and simultaneously determine sets of probability vectors (ambiguity sets) around these estimates, that contain the true transition probabilities with high confidence. We then solve a risk-averse optimal control problem that assumes the worst-case distributions in these sets. We furthermore derive a robust terminal constraint set and use it to establish recursive feasibility of the resulting MPC scheme. We validate the theoretical results and demonstrate desirable properties of the scheme through closed-loop simulations.
Investigation of Silver-Sulfur Hybrid Process for Thermochemical Hydrogen Production (1986)

A new thermochemical water-splitting process, Ag-S hybrid process, is proposed and relevant experimental results are presented. This process consists of the following three steps. 2Ag+H_2SO_4 →^^&lt;Elec.&gt; Ag_2SO_4+H_2 (R-1) Ag_2SO_4 → 2Ag+SO_3+1/20_2 (R-2) H_2O+SO_3 → H_2SO_4 (R-3) The decomposition voltage at 100 mA/cm^2 for step (R-1) was found to be 0.55 V at 353 K in 10 M H_2SO_4. The Ag_2SO_4 dissolved in H_2SO_4 could be separated by cooling. In step (R-2), Ag_2SO_4 could decompose completely in ca. 4 min at 1228 K. From a flow sheet of this process, the overall efficiency was estimated to be 31-36% with an assummed heat recovery of 70-80%.
Immunotoxicity of Therapeutic Antibodies and Nanoparticles (2020)

Therapeutic antibodies and nanotherapeutic drugs are of great concern due to their widespread use against numerous diseases worldwide. They are frequently used for targeted therapy under the assumption that they cause fewer side effects than nontargeted drugs. Despite their specificity and particular design for therapeutic actions, they might still exhibit unintended adverse effects in the immune system. Immunotoxicity reactions are mediated by immunomodulation, including immunostimulation and immunosuppression. The present review gives an overview on the adverse immunotoxic effects induced by therapeutic antibodies as well as nanotherapeutic drugs. In this context, future methods combining more efficient drug design with better tolerability and fewer adverse effects are discussed to ensure improved safety in the engineering of therapeutic antibodies and nanotherapeutics.
The Use of Infrapatellar Fat Pad-Derived Mesenchymal Stem Cells in Articular Cartilage Regeneration: A Review (2021)

Cartilage is frequently damaged with a limited capacity for repair. Current treatment strategies are insufficient as they form fibrocartilage as opposed to hyaline cartilage, and do not prevent the progression of degenerative changes. There is increasing interest in the use of autologous mesenchymal stem cells (MSC) for tissue regeneration. MSCs that are used to treat articular cartilage defects must not only present a robust cartilaginous production capacity, but they also must not cause morbidity at the harvest site. In addition, they should be easy to isolate from the tissue and expand in culture without terminal differentiation. The source of MSCs is one of the most important factors that may affect treatment. The infrapatellar fat pad (IPFP) acts as an important reservoir for MSC and is located in the anterior compartment of the knee joint in the extra-synovial area. The IPFP is a rich source of MSCs, and in this review, we discuss studies that demonstrate that these cells have shown many advantages over other tissues in terms of ease of isolation, expansion, and chondrogenic differentiation. Future studies in articular cartilage repair strategies and suitable extraction as well as cell culture methods will extend the therapeutical application of IPFP-derived MSCs into additional orthopedic fields, such as osteoarthritis. This review provides the latest research concerning the use of IPFP-derived MSCs in the treatment of articular cartilage damage, providing critical information for the field to grow.
A New Strategy toward “Simple” Water‐Soluble AIE Probes for Hypoxia Detection (2019)

Abstract Hypoxia‐responsive fluorescent probes have emerged as a novel scaffold for tumor diagnosis. However, dilemma often exists between simple synthesis and high water solubility in traditional probes. Owing to the intrinsic property of N‐oxides, herein, a new strategy is proposed to design and synthesize probes for in vitro hypoxia imaging. Equipped with tetraphenylethene (TPE), the N‐oxides exhibit aggregation‐induced emission characteristics and emit no light in aqueous solutions. Interestingly, the N‐oxides can be reduced by ferrous ions in different rates. The aggregation of the resulting hydrophobic TPE residues restricts the intramolecular motions of the molecules, which “turns‐on” their fluorescence. The NO covalent bond of one molecule can be specifically cleaved by cellular reductase overexpressed under hypoxic conditions, and thus turn‐on hypoxia imaging in vitro is achieved. The new strategy to design hypoxia imaging probes is extremely valuable and has great potential for application in tumor diagnosis.
Supplementary Figure 1 from NGF Blockade at Early Times during Bone Cancer Development Attenuates Bone Destruction and Increases Limb Use (2023)

&lt;p&gt;Supplementary Figure 1. Patella displacement is a confounding factor in bone cancer pain.&lt;/p&gt;
Treatment-resistant depression and peripheral C-reactive protein (2018)

CRP was elevated in patients with MDD, and more so in treatment-resistant patients. Other phenotypes associated with elevated CRP included childhood adversity and specific depressive and anxious symptoms. We suggest that patients with MDD stratified for proinflammatory biomarkers, like CRP, have a distinctive clinical profile that might be responsive to second-line treatment with anti-inflammatory drugs.Declaration of interestS.R.C. consults for Cambridge Cognition and Shire; and his input in this project was funded by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z). E.T.B. is employed half time by the University of Cambridge and half time by GlaxoSmithKline; he holds stock in GlaxoSmithKline. In the past 3 years, P.J.C. has served on an advisory board for Lundbeck. N.A.H. consults for GlaxoSmithKline. P.d.B., D.N.C.J. and W.C.D. are employees of Janssen Research &amp; Development, LLC., of Johnson &amp; Johnson, and hold stock in Johnson &amp; Johnson. The other authors report no financial disclosures or potential conflicts of interest.
[IC‐P‐066]: AD FAMILY HISTORY MODULATES EFFECTS OF TOMM40 ‘523’ POLY‐T ON MTL ATROPHY AND HYPOMETABOLISM IN PRECLINICAL AND AD COHORTS (2017)

There is tremendous interest in finding novel genetic risk factors for Alzheimer's disease (AD) among individuals lacking the Apolipoprotein E ε4 allele (non-APOE4's). Translocase of Outer Mitochondrial Membrane-kD40 (TOMM40), which affects mitochondrial function, is a gene with strong linkage disequilibrium to APOE. A TOMM40 variable poly-T length polymorphism at rs10524523 within intron 6 may increase risk for late onset AD. Few studies have examined how a “very long” (VL) versus “short” (S) poly-T length is related to neural outcomes. Furthermore, we found recently that AD family history (FH) changes the association between VL poly-T length and cognitive decline in cognitively normal middle-aged and aged adults across the AD spectrum. Thus, we examined TOMM40 poly-T genotype, FH, and their interaction on changes in medial temporal lobe (MTL) gray matter (GM) and glucose metabolism across time. Longitudinal linear mixed modeling assessed FH and TOMM40 main effects and interactions, among non-APOE4's, for subsets of 913 middle-aged subjects from the Wisconsin Registry for Alzheimer's Prevention (WRAP) over 7–10 years and 334 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) over 3 years. FreeSurfer was used to derive mean MTL volume and cortical thickness (CT). Arterial spin labeling (ASL) in WRAP and fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in ADNI were used to gauge MTL glucose metabolism. Significant TOMM40 x FH interactions indicated that TOMM40 VL's who were FH- and FH+ respectively showed robust step-wise protective or detrimental effects for GM, ASL, and FDG-PET. Figure 1 and Figure 2 illustrate this association in MTL volume for WRAP and MTL CT for ADNI. Figure 3 illustrates this association for MTL versus global cerebral blood flow in WRAP, with comparable associations seen for FDG-PET in ADNI.
Implementing Frequency Selective Fading for OPNET's Wireless LAN Modules (2008)

In OFDM-based IEEE 802.11 Wireless LANs, adapting the modulation type per sub-carrier to the frequency selectivity of the wireless channel leads to significant performance improvements. To integrate adaptive modulation into IEEE 802.11a/g networks, some minor modifications to the standard are needed in order to acquire the subcarrier gains and signalize the modulation assignments (on a per-packet basis), amongst others. However, to implement adaptive modulation in OPNET some changes have to be performed at the physical layer processing to include a frequency selective fading profile and to accurately compute packet error events based on the frequencyselective channel profile. We take an analytical approach for this and demonstrate a much more precise packet error behavior than with standard OPNET modules.
Experimental Study on Detecting the Omen of Flaming Phenomena in Online Social Networks: Testing the Theory of the Oscillation Model for Online User Dynamics (2019)

The explosive user dynamics including the flaming phenomena evidenced in online social networks are seriously impacting not only online communities but also social activities in the real world. Therefore, it is necessary to build a fundamental theory that can prevent or mitigate the onset of said dynamics. In our previous study, we proposed the oscillation model on networks, an attractive candidate for the fundamental theory that can describe user dynamics. Despite being born from a purely theoretical background, the theory can unify the notions of different conventional node centralities based on a common framework and provides a natural extension of node centrality. In addition, the theory can describe the explosive user dynamics. However, theory confirmation tests on experimental data has not been fully conducted yet. The theory predicts that low frequency beats are a reliable omen of the onset of explosive user dynamics. In this paper, we test the theory of the oscillation model by analyzing the logs of a Japanese major bulletin board system; the presence of low frequency beats is reported.
Super-resolution measurements with evanescent-wave fluorescence excitation using variable beam incidence (2000)

The evanescent wave (EW) elicited by total internal reflection of light selectively excites fluorophores in an optical slice above a reflecting dielectric interface. EW excitation eliminates out-of-focus fluorescence present in epiillumination microscopy, and--close to the coverslip--can offer a fivefold enhancement of axial optical sectioning compared to confocal and two-photon microscopy. The decay length of the evanescent field is a function of the refractive indices and light wavelength involved, and is modulated by the beam angle. EW microscopy was used to study the distribution and concentration of fluorophores at or near the interface in the presence of high concentrations in bulk solution. We modified an upright microscope to accommodate the condenser optics needed for EW excitation. Systematic variations of the angle of incidence were attained using an acousto-optical deflector, telecentric optics, and a hemicylindrical prism. The three-dimensional reconstruction of the fluorophore distribution from angle-resolved image stacks results in topographical information with an axial resolution of tens of nanometers. We applied this technique to study the axial position of dye-labeled subcellular storage organelles ('vesicles') of approximately 300 nm diameter in the "footprint" region of living neuroendocrine cells grown on the interface.
Usefulness of Non-detachable Balloons in Endovascular Treatment for Cerebral Aneurysms (1994)

An endovascular non-detachable balloon technique was used to treat 14 patients with cerebral aneurysms. Eight patients presented with subarachnoid hemorrhage, and six others presented with headache or mass effect. Six aneurysms were located in the anterior circulation and eight in the posterior circulation. Seven aneurysms were giant, three were large, and four were small. All target aneurysms or vessels were occluded successfully. Parent vessel was successfully spared in seven cases. There were no procedural complications related to the non-detachable nature of the balloon used. Follow-up angiography detected refilling of aneurysms in three of 11 patients, two with small ruptured aneurysms that bled again following partial deflation or balloon movement. The other aneurysms tested remained occluded, as demonstrated on follow-up angiograms, for up to 15 months. Outcomes were good to excellent in 10 patients, poor in one, and three died. Non-detachable balloons might be preferred for treatment of certain types of cerebral aneurysms including those where intraaneurysmal maneuvers might be considered dangerous, for example, with recent bleeding or intraluminal fresh clots; where precise placement of the balloon is required, for example, in the vicinity of perforators or collaterals emerging near the neck; and where detachment could be dangerous or difficult in broad neck and fusiform aneurysms or in tortuous parent vessels.
Lithographic performance results for a new 50-kV electron-beam mask writer (2001)

Current pattern generation tool designs will be inadequate to meet the advanced requirements for next-generation masks, particularly at the 100 nm node. Etec Systems, Inc. has developed a complete raster-based patterning solution to provide improved resolution, critical dimension (CD) uniformity, positional accuracy, and throughput. This solution meets the challenges of the 130-nm device generation with extendibility to at least 100 nm devices. Our complete patterning solution includes an electron-beam (e-beam) pattern generation system and a new 50 kV process. The e-beam system includes a column with 50 kV accelerating voltage and a new graybeam writing technique. To accomplish this technique, a pulse-width modulated blanking system, per-pixel deflection, retrograde scanning, and multiphase and multipass writing are used. This combination of features results in markedly improved lithographic performance and enables the use of conventional high-contrast resists for faster process implementation. Additional significant innovations of this pattern generation system include a novel stage design, an integrated automated material handling system (AMHS), on-board diagnostics, and improved environmental/thermal management. We believe this comprehensive patterning solution offers the best combination of benefits to the user in terms of versatility and extendibility.
Optimisation Strategies for Power Management of Autonomous Systems (2015)

Power requirements on autonomous systems are increasing due to rapid technology growth.Today's methods for controlling these resources use expensive and conservative strategies, or, employ pre-defined power schedules that heighten the risk of mission failure in a dynamic environment.An intelligent Power Management System (PMS) is required to improve, or maintain, system capability.My special thanks go to Peter Fleming, my primary PhD supervisor, for first awarding me with the Dorothy Hodgkin Postgraduate Award despite the 95% declaration, then providing me with excellent support, encouragement and advice, and of course for sending me off to interesting events and countries.Thanks also to Robin Purshouse, my secondary
Evolution of the microstructure in nanocrystalline copper electrodeposits during room temperature storage (2007)

The microstructure evolution in copper electrodeposits at room temperature (selfannealing) was investigated by means of X-ray diffraction analysis and simultaneous measurement of the electrical resistivity as a function of time.In-situ studies were started immediately after electrodeposition and continued with an unprecedented time resolution until stationary values of the recorded data were obtained.Independent of the copper layer thickness, the as-deposited microstructure consisted of nanocrystalline grains with orientation dependent crystallite sizes.Orientation dependent grain growth, crystallographic texture changes by multiple twinning and a decrease of the electrical resistivity occurred as a function of time at room temperature.The kinetics of self-annealing is strongly affected by the layer thickness: the thinner the layer the slower is the microstructure evolution and self-annealing is suppressed completely for a thin layer of 0.4 μm.
Advances in antibody-drug conjugates for gynecologic malignancies (2022)

Current evidence strongly supports the use of ADCs and ongoing clinical trials will provide further information into the potential of making these drugs part of current standard practice allowing patients to be treated with a higher level of personalized cancer care.
Intérêt pronostique des anticorps anti-PLA2R dans les glomérulonéphrites extra-membraneuses primitives (2014)

La présence d’anticorps circulants anti-récepteur de la phospholipase A2 (AC anti-PLA2R) est un marqueur diagnostique de la glomérulonéphrite extra-membraneuse (GEM) primitive. L’utilité pronostique des AC anti-PLA2R est toutefois encore discutée. Nous avons conduit une étude rétrospective étudiant la relation entre le taux d’AC anti-PLA2R présent au moment du diagnostic et l’évolution de la GEM. Cette étude monocentrique a inclus l’ensemble des adultes atteints de GEM primitive entre 1975 et 2007 pour lesquels du sérum prélevé au moment de la biopsie rénale et conservé à –80 °C était disponible. Le taux d’AC anti-PLA2R était rétrospectivement mesuré par test ELISA. L’association du taux d’AC avec l’activité (protéinurie et fonction rénale au diagnostic) et l’évolution (rémission et fonction rénale au dernier recul) de la GEM a été analysée (corrélation et Kaplan–Meier). Au total, 68 patients avec un recul moyen de 108 mois étaient analysés. Soixante pour cent des sujets avaient un taux d’AC anti-PLA2R positif au diagnostic. Aucune corrélation n’était retrouvée entre le taux d’AC et l’activité de la maladie ou le risque d’évolution vers l’insuffisance rénale chronique ou terminale. Cependant, un taux faible d’AC était significativement et graduellement associé à l’évolution vers la rémission spontanée (Fig. 1). Bien que le taux d’AC anti-PLA2R mesuré au diagnostic ne prédise pas l’évolution vers l’insuffisance rénale chronique de la GEM primitive, nos résultats suggèrent que ce taux pourraient permettre d’identifier précocement les patients qui vont spontanément évoluer vers la rémission.