gebhart/patrepeval huggingface dataset:
Clinical activity and safety profile of TGR-1202, a novel once daily PI3Kδ inhibitor, in patients with CLL and B-cell lymphoma. (2015)

7069 Background: TGR-1202 is a novel, next generation PI3Kδ inhibitor which lacks the hepatotoxicity associated with other PI3Kδ inhibitors and is active in patients (pts) with advanced heme malignancies (ASH 2014). Herein we present updated safety and efficacy results from a Ph I study of TGR-1202 in pts with rel/ref CLL and B-cell lymphoma. Methods: TGR-1202 is administered orally once-daily following a 3+3 dose escalation design. Eligible pts have rel/ref B-cell non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), or other B-cell malignancy and an ECOG PS ≤ 2. Endpoints: safety, PK/PD, and efficacy. Results: As of Feb 2015, 58 pts evaluable for safety including CLL, FL, Hodgkin’s (HL), DLBCL, MCL, and MZL. Median age 63 yo (range: 22-85), 72% male, ECOG 0/1/2: 19/38/1, median prior Tx: 3 (range: 1-14), 48% refractory to prior Tx. Safety: The only Gr ≥ 3 AE in ≥ 10% of pts was neutropenia (10%). AEs (all grades, all causality) in > 20% of pts were limited to diarrhea (34%), fatigue (31%), nausea (29%), and cough (26%). All diarrhea events Gr1/2, except one Gr3 event occurring in a pt in Cyc 1, which persisted for 2 days and resolved without dose interruption. Notably, in contrast to similar agents, no drug-related hepatotoxicity or colitis has been observed to date (ave time on study 7 Cyc). 2 episodes of Gr3 fatigue at 1800 mg of a new micronized formulation met the criteria for DLT. Expansion cohorts are open at 800 mg (CLL) and 1200 mg (NHL). Efficacy: A strong exposure-response relationship has been observed. Of 14 evaluable CLL pts, 13 (93%) achieved a nodal PR (median nodal ↓ of 76%), of which 7 (50%) achieved a PR per Hallek 2008 criteria. Responses have been limited in pts with aggressive lymphoma and HL. Of the 12 evaluable FL pts, 8 (67%) remain on study progression-free (range 7 - 99+ weeks), with 3 achieving a PR, notably being the 3 pts exhibiting the highest TGR-1202 plasma concentrations. Conclusions: TGR-1202 is well tolerated in pts with rel/ref heme malignancies with no reported hepatotoxicity or colitis (41% of pts on study 6+ Cyc) and promising activity in CLL and NHL. Enrollment continues in expansion cohorts. Clinical trial information: 01767766.
Improving Functional Outcome Using Compensatory Strategies in Comorbid Intellectual Disability and Psychosis: A Case Study (2013)

Relative to the general population, people with intellectual disability (ID) are at greater risk of psychosis, with an estimated prevalence of 3%–5%. By definition, ID is associated with significant impairment in adaptive function. Similarly, functional disability is a common residual feature of psychosis. Yet, reports of evidence-based treatment for functional impairment in comorbid ID and psychosis are sparse, with most literature focusing on behavior management. Given that intellectual impairment in ID and psychosis are known to interfere with functional recovery, a treatment that addresses this impairment is paramount. Cognitive adaptation training (CAT) may be a suitable intervention for this purpose, as it is underpinned by the understanding that cognitive abilities play a strong role in community functioning. CAT is a manualized intervention involving the application of multiple external compensatory strategies and environmental supports (e.g., signs, alarms, checklists) that are individually tailored based on assessment of cognition, behavioral/learning type and specific functional goals. This case study will illustrate the use of compensatory strategies and environmental supports, based on the CAT model, to address the functional goals of a young man with mild ID and first-episode psychosis.
Cerebrospinal Fluid Space Alterations in Melancholic Depression (2012)

Melancholic depression is a biologically homogeneous clinical entity in which structural brain alterations have been described. Interestingly, reports of structural alterations in melancholia include volume increases in Cerebro-Spinal Fluid (CSF) spaces. However, there are no previous reports of CSF volume alterations using automated whole-brain voxel-wise approaches, as tissue classification algorithms have been traditionally regarded as less reliable for CSF segmentation. Here we aimed to assess CSF volumetric alterations in melancholic depression and their clinical correlates by means of a novel segmentation algorithm ('new segment', as implemented in the software Statistical Parametric Mapping-SPM8), incorporating specific features that may improve CSF segmentation. A three-dimensional Magnetic Resonance Image (MRI) was obtained from seventy patients with melancholic depression and forty healthy control subjects. Although imaging data were pre-processed with the 'new segment' algorithm, in order to obtain a comparison with previous segmentation approaches, tissue segmentation was also performed with the 'unified segmentation' approach. Melancholic patients showed a CSF volume increase in the region of the left Sylvian fissure, and a CSF volume decrease in the subarachnoid spaces surrounding medial and lateral parietal cortices. Furthermore, CSF increases in the left Sylvian fissure were negatively correlated with the reduction percentage of depressive symptoms at discharge. None of these results were replicated with the 'unified segmentation' approach. By contrast, between-group differences in the left Sylvian fissure were replicated with a non-automated quantification of the CSF content of this region. Left Sylvian fissure alterations reported here are in agreement with previous findings from non-automated CSF assessments, and also with other reports of gray and white matter insular alterations in depressive samples using automated approaches. The reliable characterization of CSF alterations may help in the comprehensive characterization of brain structural abnormalities in psychiatric samples and in the development of etiopathogenic hypotheses relating to the disorders.
Structural Study ofxNa2S + (1 −x)B2S3Glasses and Polycrystals by Multiple-Quantum MAS NMR of11B and23Na (1998)

Glasses and polycrystals in the series xNa2S + (1 − x)B2S3 have been prepared and studied by magic angle spinning (MAS) NMR and by two-dimensional multiple-quantum (MQ) MAS NMR of 11B and 23Na. These techniques, when applied at various magnetic fields and combined with computer simulations of the spectra, provide new insights into the structure of the polycrystalline samples. Isotropic chemical shifts, quadrupolar parameters, and relative concentrations of the various boron sites are obtained by NMR and correlated with the known structures of boron trisulfide (x = 0), sodium metathioborate (x = 0.5) and sodium orthothioborate (x = 0.75). A structural model of polycrystalline sodium dithioborate (x = 0.33) is proposed. The MQMAS NMR method significantly enhanced the resolution in 11B spectra of xNa2S + (1 − x)B2S3 glasses and proved instrumental in finding and identifying various structural units present within these materials as the modification of the B2S3 network progressed with increasing Na2S content. The dominant 11B resonances observed in the glassy samples represent the same basic structural units that were observed in the polycrystalline compounds. In addition, several new resonances featuring trigonally and tetrahedrally coordinated boron atoms in various transitional structures between dithioborate and metathioborate, or between metathioborate and orthothioborate, were found. 23Na NMR proved less informative, especially in the glassy samples where the motion of the sodium ions between various sites precluded the observation of well-resolved spectra.
Catalytic function of DNA topoisomerase II (1991)

Although the genetic code is defined by a linear array of nucleotides, it is the three-dimensional structure of the double helix that regulates most of its cellular functions. Over the past two decades, it has become increasingly clear that aspects of this three-dimensionality which reflect topological relationships within the double helix (i.e., superhelical twisting, knotting, or tangling) influence virtually every facet of nucleic acid physiology. In vivo, DNA topology is modulated by ubiquitous enzymes known as topoisomerases. The type II enzyme is essential to the eukaryotic cell and is required for unlinking daughter chromosomes and maintaining chromosome structure. Moreover, topoisomerase II also has been identified as the primary cellular target for several widely used antineoplastic drugs. Before the physiological functions of topoisomerase II can be effectively dissected or its drug interactions fully exploited, it is imperative to understand the mechanism by which this important enzyme carries out its catalytic cycle.
Mononuclear and Binuclear Tetrapyrido[3,2-a:2‘,3‘-c:3‘‘,2‘‘-h:2‘‘‘,3‘‘‘-j]phenazine (tpphz) Ruthenium and Osmium Complexes (1996)

The monometallic complexes [(bpy)2Ru(tpphz)]2+ (4) and [(bpy)2Os(tpphz)]2+ (5), where tpphz is the poorly soluble fully aromatic tetrapyrido[3,2-a:2‘,3‘-c:3‘‘,2‘‘-h:2‘‘‘,3‘‘‘-j]phenazine, have been obtained by reaction of 5,6-diamino-1,10-phenanthroline with [(bpy)2M(phendione)]2+ (M = RuII or OsII). Reaction of 4 and 5 with metallic precursors yielded the homo- and heterobimetallic complexes [(bpy)2Ru(tpphz)Ru(NH3)4]4+ (6), [(bpy)2Ru(tpphz)Ru(bpy)2]4+ (7), [(bpy)2Os(tpphz)Os(bpy)2]4+ (8), and [(bpy)2Ru(tpphz)Os(bpy)2]4+ (9). The mononuclear 4 and 5 aggregate in solution, probably by π−π stacking of the tpphz part as shown from proton NMR. The complexes show one reversible metal-centered oxidation and several reversible (except 6) reductions which add one electron on the tpphz ligand, one electron on one bpy of each metallic end, a second electron on one bpy of each metallic end, and then a second electron on the tpphz ligand. The complexes (except 8) are luminescent in acetonitrile. Quenching of the luminescence by water has been attributed to proton quenching at the phenazine nitrogen atoms.
Quantification and Phenotypic Characterization of Extracellular Vesicles from Patients with Acute Myeloid and B-Cell Lymphoblastic Leukemia (2021)

Extracellular vesicles (EVs) act in cell-to-cell communication, delivering cargo from donor to recipient cells and modulating their physiological condition. EVs secreted by leukemic blasts in patients with leukemia have been shown to influence the fate of recipient cells in the bone marrow microenvironment. Methods to quantify and to characterize them phenotypically are therefore urgently needed to study their functional role in leukemia development and to evaluate their potential as targets for therapy. We have used cryo-electron microscopy to study morphology and size of leukemic EVs, and nanoparticle tracking analysis and fluorescence triggering flow cytometry to quantify EVs in platelet-free plasma from a small cohort of leukemia patients and healthy blood donors. Additional studies with a capture bead-based assay allowed us to establish phenotypic signatures of leukemic EVs from 17 AML and 3 B-ALL patients by evaluating the expression of 37 surface antigens. In addition to tetraspanins and lineage-specific markers we found several adhesion molecules (CD29, and CD146) to be highly expressed by EVs from B-ALL and several leukemic stem cell antigens (CD44, CD105, CD133, and SSEA-4) to be expressed by EVs from AML patients. Further improvements in analytical methods to study EVs are needed before potentially using them as biomarkers for leukemia prognosis and follow-up.
Nonlinear evolution of an interface in the Richtmyer-Meshkov instability (2003)

The linear theory of the Richtmyer-Meshkov instability derived by Wouchuk and Nishihara [Phys. Plasmas 4, 3761 (1997)] indicates that the instability is driven by the nonuniform velocity shear left by transmitted and reflected rippled shocks at a corrugated interface. In this work, the nonlinear evolution of the interface has been investigated as a self-interaction of a nonuniform vortex sheet with a density jump. The theory developed shows the importance of the finite density jump and the finite initial corrugation amplitude of the interface. By introducing Lagrangian markers on the interface with proper kinematic boundary conditions, it is shown that stretching and shrinking of the interface occur locally even in the tangential direction. This causes deformation of bubble and spike profiles depending on the Atwood number. The vorticity on the interface for a finite density jump is not conserved in the nonlinear regime. Our results suggest that the spiral structure of the spike is due to local increase and decrease of the vorticity on the interface. Nonlinear analysis shows that the large initial amplitude of the corrugation results in rapid increase of the vorticity, which may also explain the fast roll up motion of the spiral for large amplitudes. With the use of the asymptotic linear growth rate, the nonlinear evolution of the instability is uniquely determined from the initial corrugation amplitude of the interface, the Atwood number, and the incident shock intensity. There is no need to use an impulsive formulation. The analytical nonlinear growth agrees well with the experiment [Dimonte et al., Phys. Plasmas 3, 614 (1996)]. The theory reveals nonlinear properties of the instability, such as the time evolution of the interface profiles and the vorticity on the interface, and also their dependence on the Atwood number and the corrugation amplitude.
Chemical-Looping Steam Methane Reforming over a CeO2–Fe2O3 Oxygen Carrier: Evolution of Its Structure and Reducibility (2014)

Chemical-looping steam methane reforming (CL-SMR) is a promising method for the co-generation of pure hydrogen and syngas on the basis of redox cycles via a gas–solid reaction using an oxygen carrier. The performance and life of the oxygen carrier play pivotal roles in determining the feasibility and economy of the CL-SMR process. The present research was focused on the evolution of the structure and reducibility of a CeO2–Fe2O3 oxygen carrier during the CL-SMR redox process to further understand the sustainability of the oxygen carrier. The investigated CeO2–Fe2O3 complex oxide exhibited satisfactory performance in the CL-SMR process because of the chemical interaction between Ce and Fe species. A Ce–Fe–O phase equilibrium based on a stable composition of CeO2, Fe3O4, and CeFeO3 formed in the recycled samples. Surface oxygen was removed, which was accompanied by an increase in the concentration of oxygen vacancies and a decrease in the surface area of the recycled samples; these effects resulted in an increase in the high-temperature reducibility and syngas selectivity of the samples. Oxygen mobility was intensified by the Ce–Fe chemical interaction via the formation of CeFeO3 and a micromorphological transformation. These properties counteracted the sintering of the materials and guaranteed the stability of the oxygen carrier in the CL-SMR process.
Endomicroscopy and electromyography of neuromuscular junctions in situ (2014)

Our findings constitute proof-of-concept, based on live imaging in an animal model, that combining EMG/CEM may be useful as a minimally invasive precursor or alternative to motor-point biopsy in neurological diagnosis and for monitoring local administration of potential therapeutics.
Syntheses, Crystal Structures, and Spectroscopic and Magnetic Properties of [Mn2III(H2L1)(Cl4Cat)4·2H2O]∞ and [Mn2III(H2L2)(Cl4Cat)4·2CH3CN·2H2O]∞: Temperature-Dependent Valence Tautomerism in Solution (2005)

The synthesis, X-ray data, and electronic structures of two manganese(III) 1D polymers ligated by tetrachlorocatechol, [Mn(2)(III)(H(2)L(1))(Cl(4)Cat)(4).2H(2)O](infinity) (1) and [Mn(2)(III)(H(2)L(2))(Cl(4)Cat)(4).2CH(3)CN.2H(2)O](infinity) (2), are reported. The electronic structures of the complexes have been determined by UV-vis-near-IR, IR, electron paramagnetic resonance (EPR), and magnetic susceptibility measurements. Both 1 and 2 are air stable in the solid state and in solution, unlike most of the previously reported o-quinone-chelated transition-metal complexes. Electronic spectroscopy exhibits a strong near-IR band near 1900 nm for both, suggesting the presence of a mixed-valence semiquinone-catecholate oxidation state of the catechol ligands, Mn(2)(III)(Cl(4)Cat)(2)(Cl(4)SQ)(2), together with the pure catecholate forms. The presence of this isomer was further supported by EPR and magnetic susceptibility measurements. The complexes undergo intramolecular electron transfer (valence tautomerism) upon an increase of the temperature involving the equilibrium Mn(2)(III)(Cl(4)Cat)(2)(Cl(4)SQ)(2) <==> Mn(2)(II)(Cl(4)SQ)(4). This phenomenon is reversible and is studied in solution using UV-vis-near-IR spectroscopy.
Relationship of Plasma Lipid Concentrations to Fat Deposition in Pigs (1985)

The time course for changes in plasma free fatty acid and triglyceride concentration after removal of feed was established. Genetically obese and lean lines of pigs, two types of crossbred female pigs and a group of male pigs were used to establish the relationship between circulating free fatty acid or triglyceride concentrations and adiposity. Pigs were weighed, ultrasonically probed for backfat thickness, bled in a fed state and again in the fasted state. Plasma was analyzed for free fatty acid and triglyceride concentration. Fasting increased plasma free fatty acid, but only slightly increased triglyceride concentrations. There were several significant correlations between backfat thickness and plasma lipid concentrations; however, the low magnitude and inconsistency of these correlations precludes use of plasma lipid concentrations as indicators of adiposity in swine. Fasted obese pigs had lower plasma fatty acid concentrations than lean pigs at 2, 4 and 6 mo of age. If these plasma levels represent in vivo mobilization of fat, the results probably contrast with previously reported in vitro results wherein adipose tissue from obese pigs had lipolytic rates expressed on a cellular basis that were equal to or greater than those form lean pigs.
Dynamic parallelization of single-threaded binary programs using speculative slicing (2009)

The performance of single-threaded programs and legacy binary code is of critical importance in many everyday applications. However, neither can hardware multi-core processors directly speed up single-threaded programs, nor can software automatic parallelizing compilers effectively parallelize legacy binary code and irregular applications. In this paper, we propose a framework and a set of algorithms to dynamically parallelize single-threaded binary programs. Our parallelization is based on program slicing and explores both instruction-level parallelism (ILP) and thread-level parallelism (TLP). To significantly reduce the critical path of the parallel slices, our slicing algorithms exploit speculation to cut rare dependences, and use well-designed program transformations to expose parallelism. Furthermore, because we transparently parallelize binary code at runtime, we perform slicing only on program hot regions. Our experiments demonstrate that the proposed speculative slicing approach extracts more parallelism than any known slicing based parallelization schemes. For the SPEC2000 benchmarks, we can achieve 3x parallelism with infinite number of threads, and 1.8x parallelism with 4 threads.
An unsupervised language model adaptation based on keyword clustering and query availability estimation (2008)

Language model adaptation using text data downloaded from the WWW is an efficient way to train a topic-specific LM. We are developing an unsupervised LM adaptation method using data in the Web. The one key point of unsupervised Web-based LM adaptation is how to select keywords to compose the search query. In this paper, we propose a new method of selecting keywords from keyword candidates, which uses a keyword clustering technique based on word similarities. The other key point is how to determine the number of downloaded pages for each query. In this paper we propose a method to estimate “a query availability,” which is based on a small number of downloaded Web pages. The experimental result showed that the determination of downloaded pages using the query availability was effective than the conventional methods that determined the number of pages empirically.
AI Structuralist Storytelling In Computer Games (2004)

This paper is a description of our work in creating a story director agent which utilises AI techniques. The story director controls the storyline in an adventure computer game, with the player controlling the hero character, and the story director reacting to the player&amp;apos;s actions. The story is told through subplot-level plans being formulated with a case-based planner, and a social simulation system that the story director is &amp;apos;plugged in to&amp;apos;, allowing consistent logical stories while allowing for player freedom. The system has been named OPIATE – Open-ended Proppian Interactive Adaptive Tale Engine.
ChemInform Abstract: Discovery and Development of Aurora Kinase Inhibitors as Anticancer Agents (2009)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Integrin-Dependent Activation of the JNK Signaling Pathway by Mechanical Stress (2011)

Mechanical force is known to modulate the activity of the Jun N-terminal kinase (JNK) signaling cascade. However, the effect of mechanical stresses on JNK signaling activation has previously only been analyzed by in vitro detection methods. It still remains unknown how living cells activate the JNK signaling cascade in response to mechanical stress and what its functions are in stretched cells.We assessed in real-time the activity of the JNK pathway in Drosophila cells by Fluorescence Lifetime Imaging Microscopy (FLIM), using an intramolecular phosphorylation-dependent dJun-FRET (Fluorescence Resonance Energy Transfer) biosensor. We found that quantitative FRET-FLIM analysis and confocal microscopy revealed sustained dJun-FRET biosensor activation and stable morphology changes in response to mechanical stretch for Drosophila S2R+ cells. Further, these cells plated on different substrates showed distinct levels of JNK activity that associate with differences in cell morphology, integrin expression and focal adhesion organization.These data imply that alterations in the cytoskeleton and matrix attachments may act as regulators of JNK signaling, and that JNK activity might feed back to modulate the cytoskeleton and cell adhesion. We found that this dynamic system is highly plastic; at rest, integrins at focal adhesions and talin are key factors suppressing JNK activity, while multidirectional static stretch leads to integrin-dependent, and probably talin-independent, Jun sensor activation. Further, our data suggest that JNK activity has to coordinate with other signaling elements for the regulation of the cytoskeleton and cell shape remodeling associated with stretch.
Building Energy Audit Report, for Hickam AFB, HI (2010)

A building energy assessment was performed by a team of engineers from Pacific Northwest National Laboratory (PNNL) under contract to the Department of Energy/Federal Energy Management program (FEMP). The effort used the Facility Energy Decision System (FEDS) model to determine how energy is consumed at Hickam AFB, identify the most cost-effective energy retrofit measures, and calculate the potential energy and cost savings. This documents reports the results of that assessment.