gebhart/patrepeval huggingface dataset:
Topotecan and cladribine with filgrastim support in relapsed, refractory and poor prognosis leukemias: A phase I-II study (2004)

6724 Background:Patients (pts) with an antecedent hematopoietic disorder (AHD) prior to AML or with relapsed or refractory leukemias have a poor prognosis. Standard regimens are generally not curative. Topotecan, has shown activity in hematologic malignancies. It binds to topoisomerase I which results in DNA degradation and may trigger the apoptotic pathway. Cladribine (CDA), induces apoptosis in a number of malignant cell lines with effects on both dividing and quiescent cells. Responses occurred in up to 47% of pts with AML at high doses ranging up to 21 mg/m2/d with neuropathy as the dose limiting toxicity (DLT). Filgrastim (G-CSF) has reduced the frequency of infection and duration of neutropenia in pts with AML undergoing chemotherapy. Methods:Pts with poor prognosis AML or relapsed or refractory ALL, with acceptable hepatic/renal function, were entered into cohorts (3 pts/cohort) of escalating doses of topotecan and CDA each administered as a 5 day continuous infusion, according to a modified fibonacci sequence: Results: Among 24 pts entered 15 (63%) were female, 9 (37%) male with median age 61 yrs; 10 (42%) had AHD; 4 (17%) secondary AML, 13 (54%) relapsed AML, and 2 (8%) relapsed ALL. Responses occurred in 7 (35%) of 20 evaluable pts: 4 CR, 1 CRp, 2 PR, 13 NR and 4 inevaluable. Duration of response ranged up to 22 months. No grade 4 non-hematologic toxicities were identified. Grade 4 cytopenias occurred in all. One pt in cohort 5 had persistent marrow hypoplasia at day 34 and succumbed to sepsis on day 48, potentially representing a DLT. Treatment associated mortality (TAM) is 12%. Conclusions:The combination is well tolerated and appears active. The TAM is well within the range reported in this heavily treated population. Once an MTD is established, incorporation of this regimen as a component of other treatment strategies should be explored. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline Amgen GlaxoSmithKline; Ortho Biotech; Amgen
Superdistribution: Objects As Property on the Electronic Frontier (1995)

Chapter 1. Information Revolution. Computers, Communications, and Mankind. Invisible Plumbing. Breadth Versus Depth. The Electronic Frontier. The Largest Upheaval of All. Taming the Electronic Frontier. Indigenous Encounters on the Electronic Frontier. 2. Structure of Production. The Tale of the Wooden Pencil. Structure of Production. Social Binding Forces. Commercial Exchange Transactions. The Lair of the Software Werewolf. Pencils as the Fruit of the Pencil Tree. Indian Pottery. Electronic Pencils. Software ICs. Summary. 3. Software Crisis. The Good News: There is a Silver Bullet. The Bad News: Silver Bullets are Paradigm Shifts, Not Tools. The Copernican Revolution. Software Complexity. Software Industrial Revolution. The Intangibility Imperative. Process-Centric Versus Product-Centric. The Structure of Scientific Revolutions. Software Industrial Revolution. Essence Versus Accidents of Software Engineering. The Four Obstacles. Robust Economics for Information- Age Goods. Summary. 4. Software Architecture. What, If Anything, is an Object. Heterogeneity. Compositional Architectures. System 12. Fabrication and Assembly. Specialization of Labor. Process Versus Product. Encapsulation and the Law of Proximity. Programming Languages and Operating Systems. A Richer Set of Architectural Distinctions. Five Architectural Levels by Example. Technical Definitions. Process-level Objects. Task-level Objects. Chip-level Objects. Block- and Gate-level Objects. Programming Language Comparison. Summary. 5. Industrial Revolution. Specification, Testing, and Language. Specification and Testing Tools. Armory Practice. Thomas Jefferson. Eli Whitney. Roswell Lee. Revolutions Dont Happen Overnight. The Heroes of the Industrial Revolution. Software Engineering. Specification and Testing Tools. What is a Stack. Assertion Checking. White-Box Testing. Black-Box Testing. Black-Box Specification/Testing. Classes and Inheritance. 6. Out of the Crisis. Out of the Crisis.
Ascorbate oxidation is a prerequisite for its transport into rat liver microsomal vesicles (2000)

Oxidation and uptake of ascorbate show similar time courses in rat liver microsomal vesicles: a rapid burst phase is followed by a slower process. Inhibitors of ascorbate oxidation (proadifen, econazole or quercetin) also effectively decreased the uptake of ascorbate. The results show that dehydroascorbate is the transport form of ascorbate at the membrane of the endoplasmic reticulum.
T1 Hypoxia-Inducible Factor 2α Regulates Neutrophilic Inflammation in Humans, Mice and Zebrafish (2012)

Neutrophilic inflammation plays an important role in inflammatory lung diseases but therapeutic targeting of neutrophil (PMN) persistence is lacking. PMN lifespan and function is regulated by hypoxia, a characteristic feature of inflamed tissues, via the HIF/VHL/hydroxylase pathway, specifically hypoxia inducible factor-1α (HIF-1α) and prolyl hydroxylase-3 (PHD3). Targeting HIF-1α in myeloid cells impaired immune function, but PHD3 regulated PMN lifespan without affecting function. Given that PHD3 preferentially regulates HIF-2α, we investigated the role of HIF-2α in PMN-mediated inflammation. Peripheral blood PMNs isolated from healthy volunteers and mice expressed HIF-2α and expression was enhanced by heat-killed bacteria. Using PMNs isolated from patients with active inflammatory arthritis (IA) we demonstrated significant upregulation of <i>HIF2A</i> mRNA (IA 92.9±30.3 vs. control 4.3±0.9 AU relative to <i>ACTB</i>, <i>P</i>&lt;0.05) and protein (IA 0.26±0.05 vs. control 0.01±0.01 OD relative to P38, <i>P</i>&lt;0.01) in circulating inflammatory PMNs. PMNs recruited to the airways of patients with COPD also displayed strong HIF-2α staining. The consequences of HIF-2α upregulation were examined using human PMNs from patients with gain-of-function mutations in the <i>HIF2A</i> gene. Neutrophils isolated from these patients had reduced rates of constitutive apoptosis. Recapitulation of the human <i>HIF2A</i> mutations in the orthologous <i>HIF2A</i> gene, <i>epas1a</i>, in zebrafish delayed resolution of inflammation in a tail injury model (24 hrs post injury, <i>epas1a</i> 12.7±1.4 vs. ctrl 5.2±0.5 PMNs, p&lt;0.001) with an associated reduction in PMN apoptosis (<i>epas1a</i> 1.0% vs. ctrl 1.6%, p&lt;0.05). Mice with myeloid-specific deletion of <i>Hif2a</i> had normal PMN survival in response to hypoxia and the cells showed no functional defect <i>in vitro</i>. Importantly, in a PMN-mediated acute lung injury model, myeloid-specific deficiency of HIF-2α markedly enhanced resolution of inflammation (BAL PMN count 48 hours following nebulised LPS, WT<i></i> 2.13×10<sup>6</sup>±0.08 vs. KO 1.39×10<sup>6</sup>±0.24, p&lt;0.05) and reduced lung injury (BAL IgM at 48 hours, WT 211±22.8 vs. KO 74.7±27.2 ng/ml), implicating HIF-2α in PMN persistence in inflamed lung tissue. These data support a critical and selective role for HIF-2α in the resolution of inflammation through the maintenance of PMN survival, and provide a platform to dissect the therapeutic utility of targeting HIF-2α in chronic inflammatory diseases.
Citrus Packaging and the Environment (1990)

Say the word “environment” today, and most likely you will generate some sort of a response. It’s one of our society’s hot issues and we have seen Washington, from President Bush on down, and many of our states and cities jumping on the environmental issue because there are real problems that need to be solved and, in addition, it appears to be good politics. Solid waste is part of the environmental issue and packaging is part of solid waste. So, I would like to take you through how we, at Continental Can, are looking at this. We are one of the leading packaging producers with seven domestic divisions producing aluminum cans, steel and bi-metal cans, PET plastic bottles, extrusion blow molded plastic bottles from HDPE, PP, PVC, with multilayers and multimaterial barriers, and thermo formed microwave trays and tubs and aseptic cups mostly made from plastic multimaterial barrier sheet which we extrude. Continental also annually produces over 6 billion metal vacuum “twist off” closures, some plastic closures and our Bondware division produces paper and plastic coated paper containers mostly or fast food outlets. Paper published with permission.
High resolution broad-band spectroscopy in the NIR using the Triplespec externally dispersed interferometer at the Hale telescope (2014)

High resolution broad-band spectroscopy at near-infrared wavelengths has been performed using externally dis- persed interferometry (EDI) at the Hale telescope at Mt. Palomar. The EDI technique uses a field-widened Michelson interferometer in series with a dispersive spectrograph, and is able to recover a spectrum with a resolution 4 to 10 times higher than the existing grating spectrograph. This method increases the resolution well beyond the classical limits enforced by the slit width and the detector pixel Nyquist limit and, in principle, decreases the effect of pupil variation on the instrument line-shape function. The EDI technique permits arbi- trarily higher resolution measurements using the higher throughput, lower weight, size, and expense of a lower resolution spectrograph. Observations of many stars were performed with the TEDI interferometer mounted within the central hole of the 200 inch primary mirror. Light from the interferometer was then dispersed by the TripleSpec near-infrared echelle spectrograph. Continuous spectra between 950 and 2450 nm with a resolution as high as ~27,000 were recovered from data taken with TripleSpec at a native resolution of ∼2,700. Aspects of data analysis for interferometric spectral reconstruction are described. This technique has applications in im- proving measurements of high-resolution stellar template spectra, critical for precision Doppler velocimetry using conventional spectroscopic methods. A new interferometer to be applied for this purpose at visible wavelengths is under construction.
Physicochemical qualities and ingestibility of high value-added amlodipine besilate formulations (2016)

Objectives The physicochemical qualities and ingestibility of high value-added amlodipine besilate formulations were evaluated using one brand name and four generic orally disintegrating tablets (formulations A, B, C, D, and E) and a generic orally disintegrating film (formulation F). Methods Pushing out from a press-through package, tablet strength, and hydrophilia were examined for the aforementioned formulations A–E, and sensory characteristics according to the disintegration time, taste, and palatability in healthy subjects were evaluated for formulations A–F. Results The strength required for pushing out from a press-through package for formulations A, B, C, D, and E was approximately 20 N, indicating ease of opening for most users. Moreover, hardness and friability of formulations A, B, C, D, and E were more than 0.03 kg/mg and less than 1%, respectively. Thus, all formulations had sufficient tablet strength to endure fall impact in the automatic packing machine and vibration when carrying them from one place to another. The wetting time of formulation E (9 s) was significantly shorter than that of formulations A (27 s), B (34 s), C (28 s), and D (29 s), indicating that with the exception of hydrophilia, the physicochemical qualities of the five aforementioned formulations of orally disintegrating tablets were equivalent. The disintegration time of formulations E (15 s) and F (15 s) in the oral cavity was significantly shorter than that of formulations A (23 s), B (26 s), C (25 s), and D (22 s). Moreover, more than 50% of subjects reported strong or weak bitterness for formulations B, C, D, E, and F. Finally, more than 80% of subjects described formulations A, E, and F as easy to take, indicating good palatability. Conclusions This study provides useful information for selecting high value-added amlodipine besilate formulations for individualized treatments.
Sleepiness and fatigue in multiple sclerosis - same same but different? A systematic review on the Epworth Sleepiness Scale as an assessment tool (2016)

Objectives: Fatigue is a frequent and distressing symptom in patients with multiple sclerosis (MS). In contrast, sleepiness, characterized by difficulties to stay awake and alert during the day, seems to be less prevalent in MS; however exact studies are lacking. In addition, there is a semantic confusion of the concepts of “fatigue” and “sleepiness”, which are often used interchangeably. Methods: We conducted a systematic review of studies using the Epworth Sleepiness Scale (ESS) for the assessment of daytime sleepiness in patients with MS. Results: The summarized results of 48 studies demonstrate that sleepiness, as indicated by elevated ESS scores, is less prevalent and less severe than fatigue but is present in a significant proportion of patients with MS. In most cross-sectional and longitudinal studies, there was a moderate association between ESS scores and various fatigue rating scales. Longitudinal studies on the effect of wakefulness- promoting agents failed to show a consistent improvement of sleepiness or fatigue as compared to placebo. It has also been shown that daytime sleepiness is frequently associated with comorbid sleep disorders that are often underrecognized and undertreated in MS. Conclusions: Sleepiness and potential sleep disorders may also precipitate and perpetuate fatigue in patients with MS and should be part of the differential diagnostic assessment. To support an appropriate decision-making process, we propose an algorithm for the evaluation of sleepiness as compared to fatigue in patients with MS. Disclosure: Nothing to disclose.
A Stable Three-Coordinate Rhodium(I) Olefin Complex (1998)

Reaction of LLi (L = ArNC(Me)CHC(Me)NAr, Ar = 2,6-Me2C6H3) with [Rh(COE)2Cl]2 (COE = cyclooctene) produces stable, three-coordinate LRh(COE) (1). At room temperature in solution, the LRh fragment moves rapidly over one face of the COE ligand via reversible allyl hydride formation.
Quantification of memory in fractional-order capacitors (2019)

Abstract In this study we quantify and interpret the inherent memory in fractional-order capacitors when subjected to constant current charging/discharging waveforms. This is done via a finite difference approximation of the fractional order rate equation relating current to voltage in these devices. It is found that as the fractional exponent decreases, the weight of the voltage memory trace that results from the contribution of past voltage activity increases, and thus the measured response of the device at any time is increasingly correlated to its past. Ideal capacitors, on the other hand, which are described by the first order differential equation , do not exhibit such behavior and are memoryless devices.
Effect of Sildenafil on Diabetic Gastropathy (2002)

Diabetic gastropathy (DG) is the most serious neuromuscular dysfunction of the stomach that may affect diabetic patients. DG is a syndrome of delayed gastric emptying correlated to alterations of gastric tone, contractility, and myoelectrical activity. Gastric dysrhythmias, antral hypomotility, antral dilation, antroduodenal incoordination, and pylorospasm variously relate to DG.

DG pathogenesis is multifactorial: autonomic neuropathy, microangiopathy, and the degenerative impairment of gastric neuromuscular structure are possible mechanisms of gastric dysfunction. Also, the acute increase in blood glucose might reversibly delay gastric emptying (1,2). Gastric dysrhythmias correlate with a disturbance of gastric electrical slow waves (ESWs). ESW rhythm, which is generated by interstitial cells of Cajal, coordinates gastric peristalsis (3,4). Cajal cells, distributed in specific locations …
A Mechanical Device for Controlling the Radial Intensity Distribution of a Light Beam (1972)

A device is described which produces a beam of light which, time averaged, is axially symmetrical in intensity. Results are given which show that the intensity distribution can be controlled to within ½% of a desired symmetrical distribution.
Fundamental Aspects of Metal-Ion Separations by Centrifugal Partition Chromatography (1999)

Centrifugal partition chromatography (CPC), a multistage countercurrent liquid-liquid distribution technique employing discrete stages and two immiscible bulk liquid phases, is ideally suited for the detailed examination, through evaluation of separation factors and efficiencies, of the influence of bulk aqueous and liquid-liquid interfacial equilibria and kinetics on the separations of metal ions. This has been demonstrated by studies of the separation of transition metals, platinum group metals, and trivalent lanthanides. The results indicate that separation efficiencies in CPC are mainly limited by back-extraction kinetics that occur in the bulk aqueous phase and at the organic-aqueous interface as indicated by a direct linear correlation between the half-lives (t1/2's) of the dissociation reactions and the reduced plate height. In addition, the interfacial areas calculated through this correlation are much larger in many cases thanthose generated in highly stirred two phase mixtures. Finally, addition of surfactants and interfacial catalysis of the formation and dissociation of the complexes dramatically improve efficiencies.
Assessment of multiple displacement amplification in molecular epidemiology (2004)

Well-characterized epidemiological resources are generated with great effort, yet associated patient DNA samples can be limiting. The efficacy of the whole genome amplification (WGA) method, termed multiple displacement amplification (MDA), was assessed for detecting heterozygous sequence variants, mutation scanning, and PCR for challenging segments. Fifteen common polymorphisms from 10 genes located on 8 chromosomes were genotyped by direct sequencing of 300 PCR products from 115 high-quality MDA-amplified DNA samples extracted by different methods. The GC content of these analyzed segments ranges from 30% to 69%. Genotyping results demonstrate 100% accuracy. For heterozygotes, the relative intensity of peaks generated by the two alleles is highly similar for genomic and MDA-amplified genomic DNA, independent of GC content. In contrast, one of four heterozygous loci was mistyped when lower quality MDA-amplified DNA samples were used. The results of single-stranded conformation polymorphism (SSCP)-type of mutation scanningfor seven MDA-amplified DNA samples in four genes were concordant with the genomic DNA samples. PCR on MDA-amplified DNA was routinely successful for challenging 10- and 12-kb segments with GC content ranging from 30% to 80%, demonstrating that rather long segments, which are difficult to amplify with PCR, are amplified well with MDA. These results suggest that MDA is an effective method of WGA with utility in molecular epidemiology. Quality control of the MDA-amplified DNA is critical for high performance.
Control of Active and Reactive Power Ripple to Mitigate Unbalanced Grid Voltages (2015)

Managing power delivery from distributed generation systems is challenging when the grid voltages are unbalanced, since the negative sequence voltage causes power oscillations at twice the fundamental grid frequency. Current regulation using sequence components can be used to manage these real and reactive power oscillations, and thus help mitigate the unbalanced network voltages. This paper presents a consolidated control scheme using double sequence frame current regulators that can readily adjust between eliminating real or reactive power oscillations created by unbalanced grid voltages, or alternatively can simply balance the three-phase currents. The mitigation influence of these alternative control strategies on unbalanced grid voltages is then experimentally examined for a distribution feeder with a resistive and/or reactive series impedance.
In vivo manipulation (depletion versus activation) of testicular macrophages: central and local effects (1996)

Testicular macrophages are a relevant cell type for the regulation of Leydig cell steroidogenesis. The availability of liposome technology allows in vivo manipulation of macrophages in order to analyze their role in the regulation of the hypothalamic-pituitary-testicular axis. In this study, adult (70 days of age) and prepubertal (22 days of age) rats were injected intratesticularly with liposomes containing either dichloromethylene diphosphonate (C12MDP) to deplete testicular macrophages or muramyl tripeptide (MTP-PE) to activate them. Control rats were injected with the corresponding volumes of 0.9% NaCl. Animals were killed 10 days after treatment. Adult rats injected bilaterally or unilaterally with C12MDP liposomes showed increased serum LH and testosterone concentrations, as well as increased testosterone concentrations in the testicular interstitial fluid. In unilaterally injected rats, testosterone concentrations in the interstitial fluid were higher in the macrophage-containing testes than in the contralateral, macrophage-depleted testes. Adult rats treated bilaterally with MTP-PE liposomes showed increased numbers of testicular macrophages, whereas the number of Leydig cells was unchanged. Serum LH concentrations were decreased, but no changes were found in testosterone concentrations. Prepubertal rats treated bilaterally with C12MDP liposomes showed decreased numbers of Leydig cells. However, serum LH and testosterone concentrations were increased. Otherwise, prepubertal rats treated bilaterally with MTP-PE liposomes showed increased numbers of macrophages and Leydig cells, as well as increased serum testosterone concentrations. These data suggest that testicular macrophage-derived factors act at two different levels in the pituitary-testicular axis: first, at a central level by inhibiting LH secretion, and secondly, at a local level by stimulating Leydig cell steroidogenesis.
Speech Recognition and Comfort Using Hearing Instruments with Adaptive Directional Characteristics in Asymmetric Listening Conditions (2005)

It is concluded that bilateral hearing instruments with adaptive directional microphones confer benefits in terms of speech recognition in noise and sound quality. Independence of the two adaptive control systems does not appear to cause untoward effects.
Ablation and Microstructure Imaging of Dentin-Enamel Junction Using Focused Electron Beam in an Environmental Scanning Electron Microscope (2018)

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