gebhart/patrepeval huggingface dataset:
Characterizing nanoparticle interactions: Linking models to experiments (2000)

Self-assembly of nanoparticles involves manipulating particle interactions such that attractions are on the order of the average thermal energy in the system. If the self-assembly is to result in an ordered packing, an understanding of their phase behavior is necessary. Here we test the ability of simple pair potentials to characterize the interactions and phase behavior of silico tungstic acid (STA), a 1.2 nm particle. The strength of interaction is controlled by dispersing STA in different background salt concentrations. The experimental variables used in characterizing the interactions are the osmotic compressibility (dΠ/dρ), the second virial coefficient (B2), relative solution viscosity (η/ηc), and the solubility (ρσ3)sat. Various techniques are then developed to extract the parameters of square well, the adhesive hard sphere (AHS), and the Yukawa pair potentials that best describe the experimental data. The AHS model describes the solution thermodynamic behavior only where the system is weakly attractive but, as would be expected, fails when long range repulsions or nonmonotonic pair potentials become important. Model free representations are presented which offer the opportunity to extract pair potential parameters.
Fetal hemoglobin induction with butyric acid: efficacy and toxicity (1993)

Butyric acid induces fetal hemoglobin (HbF), a property of potential therapeutic advantage in patients with disorders of globin chain synthesis. We performed dose escalation studies of this compound in baboons to assess whether clinically significant increases in HbF are achievable, and to define the associated toxicities. Additionally, the effect of butyrate in combination with erythropoietin on HbF induction was assessed. HbF induction in response to butyrate was dependent on the dose and duration of treatment. Doses of butyrate less than 4 g/kg/d were associated with minimal toxicity (hypokalemia) and significant HbF induction in these nonanemic animals, with 1 g/kg/d producing an increase in HbF-containing reticulocytes (F reticulocytes) from 0.9% to 8.7% and an increase in HbF from 0.8% to 1.4%. A dose of 2 g/kg/d resulted in an increase in F reticulocytes from 2.1% to 27.8% and an increase in HbF from 0.7% to 2.2%. Doses of 4 g/kg/d in another animal produced an increase in F reticulocytes from 1% to 21.6% and in HbF from 1.9% to 5.3%. Infusions in excess of 4 g/kg/d were complicated (after a variable amount of time) by a decreased level of alertness (caused by hyperosmolality or butyrate itself) and hematologic toxicity (with declines in reticulocyte, white blood cell, and platelet counts). Prolonged infusions of high doses of butyrate (8 to 10 g/kg/d) were associated with peak F reticulocyte percentages reaching 38% to 64.5% and HbF reaching levels in excess of 20%. These high doses (8 to 10 g/kg/d) were complicated in two animals with a striking and unique neuropathologic picture and, in one animal, multiorgan system failure. Erythropoietin in combination with butyrate, induced F reticulocytosis in an additive manner. We conclude that butyric acid is a strong inducer of HbF, particularly when administered in combination with erythropoietin. As chronic toxicities remain undefined, patients in future clinical trials of this and similar compounds should be monitored closely for evidence of neurologic toxicity.
Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications (2002)

Thalidomide (Thal) achieves responses even in the setting of refractory multiple myeloma (MM). Although increased angiogenesis in MM bone marrow and the antiangiogenic effect of Thal formed the empiric basis for its use in MM, we have shown that Thal and its immunomodulatory analogs (IMiDs) directly induce apoptosis or growth arrest of MM cells, alter adhesion of MM cells to bone marrow stromal cells, inhibit the production of cytokines (interleukin-6 and vascular endothelial growth factor) in bone marrow, and stimulate natural killer cell anti-MM immunity. In the present study, we demonstrate that the IMiDs trigger activation of caspase-8, enhance MM cell sensitivity to Fas-induced apoptosis, and down-regulate nuclear factor (NF)-kappa B activity as well as expression of cellular inhibitor of apoptosis protein-2 and FLICE inhibitory protein. IMiDs also block the stimulatory effect of insulinlike growth factor-1 on NF-kappa B activity and potentiate the activity of TNF-related apoptosis-inducing ligand (TRAIL/Apo2L), dexamethasone, and proteasome inhibitor (PS-341) therapy. These studies both delineate the mechanism of action of IMiDs against MM cells in vitro and form the basis for clinical trials of these agents, alone and coupled with conventional and other novel therapies, to improve outcome in MM.
Experimental simulation evaluation of ECG‐gated heart scans with a small number of views (1983)

Computed tomography (CT) scanning techniques designed to visualize the beating heart utilize the electrocardiogram (ECG) waveform to gate or select the phase of the cardiac cycle being imaged. Most such methods require that each slice to be imaged be scanned many times to obtain the usual number of projections in a single phase interval of the cardiac cycle. We are studying a new method in which only a single scan of 20 s should be required per imaged slice. The central problem in the proposed technique is to test the diagnostic utility of images reconstructed from a very limited number (about 25) of projections. An essential part of the proposed algorithm is the elimination of all material outside a circle chosen to contain only the heart and the structures immediately surrounding it. Experiments are reported here on scans of calf's heart in an 11-cm container of water, with most views deleted so as to simulate the results from this type of gated scan. The results show that if no high-contrast objects are within the chosen circle, then image quality is satisfactory and could be clinically useful.
A Wireless Multi-Channel Recording System for Freely Behaving Mice and Rats (2011)

To understand the neural basis of behavior, it is necessary to record brain activity in freely moving animals. Advances in implantable multi-electrode array technology have enabled researchers to record the activity of neuronal ensembles from multiple brain regions. The full potential of this approach is currently limited by reliance on cable tethers, with bundles of wires connecting the implanted electrodes to the data acquisition system while impeding the natural behavior of the animal. To overcome these limitations, here we introduce a multi-channel wireless headstage system designed for small animals such as rats and mice. A variety of single unit and local field potential signals were recorded from the dorsal striatum and substantia nigra in mice and the ventral striatum and prefrontal cortex simultaneously in rats. This wireless system could be interfaced with commercially available data acquisition systems, and the signals obtained were comparable in quality to those acquired using cable tethers. On account of its small size, light weight, and rechargeable battery, this wireless headstage system is suitable for studying the neural basis of natural behavior, eliminating the need for wires, commutators, and other limitations associated with traditional tethered recording systems.
Enantiomeric perylene-glycerolipids as fluorogenic substrates for a dual wavelength assay of lipase activity and stereoselectivity (1996)

A new type of fluorogenic alkyldiacyl glycerols was synthesized and used as fluorogenic substrates for the analysis of lipase activities and stereoselectivities. These compounds contain perylene as a fluorophore and the trinitrophenylamino (TNP) residue as a quencher. Both substituents are covalently bound to the omega-ends of the sn-2 and sn-1 (3) acyl chains, respectively. Upon glycerolipid hydrolysis, the residues are separated from each other thus allowing determination of lipase activity by the continuous increase in fluorescence intensity which is caused by dequenching. Using enantiomeric pairs of these compounds, we were able to analyze lipase stereoselectivity depending on the reaction medium. Mixtures of enantiomeric fluorogenic alkyldiacyl glycerols, selectively labelled with pyrene or perylene as fluorophores, can be used for a dual-wavelength "stereoassay" of lipases. Since absorption and emission maxima of both labels are clearly separated, hydrolysis of the respective enantiomeric substrates can be determined simultaneously, and the difference in the rates of hydrolysis can be taken as a parameter for the stereopreference of a lipase. Hydrolysis rates measured with perylene-substituted lipids are generally lower than those obtained with the pyrene analogs. Thus, with a mixture of perylene and pyrene-substituted lipids, we observe a higher apparent stereoselectivity of lipases since we measure a combination of stereo- and substrate selectivity. In the presence of albumin, all microbial lipases tested so far exhibit stereopreference for the sn-1 glycerol position. In our assay, the apparent stereoselectivities are highest if in the presence of albumin, the sn-1 position carries pyrene and the sn-3 position is substituted with perylene. The lipase stereoselectivity assay described here requires the simultaneous measurement of the fluorescence intensities at two different wavelengths in a single cuvette and can thus be carried out using existing and cheap instrumentation that was developed for the fluorimetric analysis of Ca+2 concentrations.
Evaluation of small-angle scattering data from lamellar and cylindrical particles by the indirect transformation method (1980)

The cross-section scattering function and the cross-section distance distribution function are of special interest when lamellar or cylindrical particles are investigated by small-angle scattering techniques with high resolution. These functions can be computed from the unsmoothed, smeared scattering data by the indirect transformation method. This method requires an estimate for the maximum cross-section dimension, which can be found from the distance distribution function of the particle. The influence of finite size, the termination effect and the limits of resolution are discussed using results from simulated experiments.
Requirement of Hippocampal Neurogenesis for the Behavioral Effects of Antidepressants (2003)

Various chronic antidepressant treatments increase adult hippocampal neurogenesis, but the functional importance of this phenomenon remains unclear. Here, using genetic and radiological methods, we show that disrupting antidepressant-induced neurogenesis blocks behavioral responses to antidepressants. Serotonin 1A receptor null mice were insensitive to the neurogenic and behavioral effects of fluoxetine, a serotonin selective reuptake inhibitor. X-irradiation of a restricted region of mouse brain containing the hippocampus prevented the neurogenic and behavioral effects of two classes of antidepressants. These findings suggest that the behavioral effects of chronic antidepressants may be mediated by the stimulation of neurogenesis in the hippocampus.
White organic light-emitting devices using a phosphorescent sensitizer (2003)

The efficiency of white organic light-emitting devices has been improved dramatically by the introduction of a phosphorescent material, fac tris (2-phenylpyridine) iridium [Ir(ppy)3] as a sensitizer. Ir(ppy)3 and 4-(dicyanomethylene)-2-t-butyl-6-(1,1,7,7-tetramethyljulolidyl-9-enyl) are codoped into 4,4′-N,N′-dicarbazole-biphenyl (CBP) host. The chromaticity of white emission can be tuned by adjusting the thickness of the codoped CBP layer or the concentration of Ir(ppy)3. The luminance efficiency of these devices is affected at the same time due to the severe difference in efficiency between the two primary emission peaks.
Structural basis of calcium and galactose recognition by the lectin PA‐IL of Pseudomonas aeruginosa (2003)

The structure of the tetrameric Pseudomonas aeruginosa lectin I (PA-IL) in complex with galactose and calcium was determined at 1.6 A resolution, and the native protein was solved at 2.4 A resolution. Each monomer adopts a beta-sandwich fold with ligand binding site at the apex. All galactose hydroxyl groups, except O1, are involved in a hydrogen bond network with the protein and O3 and O4 also participate in the co-ordination of the calcium ion. The stereochemistry of calcium galactose binding is reminiscent of that observed in some animal C-type lectins. The structure of the complex provides a framework for future design of anti-bacterial compounds.
A phase II, open-label pilot study evaluating the safety and activity of nal-IRI in combination with 5-FU and oxaliplatin in preoperative treatment of pancreatic adenocarcinoma (NEO-Nal-IRI study). (2019)

TPS476 Background: Neoadjuvant treatment for borderline resectable pancreatic cancer (PCa) is increasing in acceptability, but a standard regimen has yet to be established. Multiple studies have demonstrated feasibility and effectiveness of the FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen in the perioperative setting. However, FOLFIRINOX often requires dose modifications, delays and growth factor support due to excessive toxicity which can complicate care delivery when given neoadjuvantly. Irinotecan liposomal injection (Nal-IRI) is FDA approved with a very tolerable safety profile in refractory metastatic PCa. The current study aims to substitute Nal-IRI for traditional irinotecan in the standard FOLFIRINOX regimen and demonstrate safe and effective delivery in the neoadjuvant setting. Methods: This phase II, open-label, single-arm study targets patients with borderline resectable PCa without metastatic disease. Other key eligibility criteria include age ≥ 18 years, measurable disease by RECIST v1.1, adequate cardiac, renal, hepatic function, and Eastern Cooperative Oncology Group performance status of 0 to 1. Patients receive FOLFNal-IRINOX regimen as per table every two weeks for four months followed by disease reassessment. Patients who remain surgical candidates will undergo surgical resection within four to eight weeks following last dose of therapy. The primary endpoint is to assess safety and feasibility of regimen in perioperative setting. Secondary endpoints include R0 resection rate, clinical, biochemical and radiological response rate and patient-reported quality of life as measured by the NCI validated FACT-G scale. Enrollment continues to a maximum of 28 evaluable patients to demonstrate a reduction in historical 30 day postoperative complication rate. FOLFNal-IRINOX regimen. Clinical trial information: NCT03483038. [Table: see text]
Assessment of cognitive fluctuation in dementia: a systematic review of the literature (2012)

We conclude that further research is warranted into the assessment of CF, and this is timely given the increasing recognition of the clinical importance of CF as a dementia symptom, particularly in the Lewy body dementias.
The MOS 36-ltem Short-Form Health Survey (SF-36): III. Tests of Data Quality, Scaling Assumptions, and Reliability Across Diverse Patient Groups (1994)

The widespread use of standardized health surveys is predicated on the largely untested assumption that scales constructed from those surveys will satisfy minimum psychometric requirements across diverse population groups. Data from the Medical Outcomes Study (MOS) were used to evaluate data completeness and quality, test scaling assumptions, and estimate internal-consistency reliability for the eight scales constructed from the MOS SF-36 Health Survey. Analyses were conducted among 3,445 patients and were replicated across 24 subgroups differing in sociodemographic characteristics, diagnosis, and disease severity. For each scale, item-completion rates were high across all groups (88% to 95%), but tended to be somewhat lower among the elderly, those with less than a high school education, and those in poverty. On average, surveys were complete enough to compute scales scores for more than 96% of the sample. Across patient groups, all scales passed tests for item-internal consistency (97% passed) and item-discriminant validity (92% passed). Reliability coefficients ranged from a low of 0.65 to a high of 0.94 across scales (median = 0.85) and varied somewhat across patient subgroups. Floor effects were negligible except for the two role disability scales. Noteworthy ceiling effects were observed for both role disability scales and the social functioning scale. These findings support the use of the SF-36 survey across the diverse populations studied and identify population groups in which use of standardized health status measures may or may not be problematic.
Role of murine tumor models in cancer treatment research. (1986)

Two major factors have contributed to a widely held disenchantment with murine tumor models for drug screening in cancer research: (a) the higher costs of these models in comparison to studies performed with tumor cells in vitro; and (b) the perception that these models have failed to demonstrate satisfactory correlation of chemosensitivity with analogous human tumor types; i.e., murine tumors generally have proved to be sensitive to many more agents than are found to be active in the clinic. The perceived failure of the murine models is discussed with particular reference to the difference in criteria used for evaluating drug sensitivity in murine tumor models versus clinical trials, and we conclude that the perception about murine models is not tenable in light of present information. The very important role of murine tumor models in optimizing dosage and administration schedules and, most importantly, in the development of a new drug to its most useful potential in combination chemotherapy is discussed. The value of this in vivo methodology is stressed.
Experimental therapeutics with a new 10-deazaaminopterin in human mesothelioma: further improving efficacy through structural design, pharmacologic modulation at the level of MRP ATPases, and combined therapy with platinums. (2001)

Studies described here sought to evaluate the therapeutic potential of a new 10-deazaaminopterin analogue, 10-propargyl-10-deazaaminopterin (PDX), alone and in combination with platinum compounds in the treatment of human pleural mesothelioma. In vitro studies documented 25-30-fold and 3-fold, respectively, greater cytotoxic potency of PDX compared with methotrexate and another 10-deazaaminopterin, edatrexate, against VAMT-1 and JMN cell lines derived from human mesothelioma. These tumor cell lines were also inhibited by platinum compounds. Cisplatin (CDDP) was somewhat more inhibitory than oxaloplatin and >1 log order in magnitude more inhibitory than carboplatin (CBCDA). Against the JMN tumor xenografted in nude mice, whereas methotrexate and, more so, edatrexate, were potently growth inhibitory, only PDX brought about substantial regression. By comparison, CDDP and CBCDA, but not oxaloplatin were markedly growth inhibitory to this same tumor in vivo. This high level of therapeutic activity of PDX could be additionally enhanced by coadministration of probenecid, an inhibitor of canicular multispecific organic anion transporter/multidrug resistance-related protein (MRP)-like ATPases, which increased the number of complete regressions by >-3 fold. Canicular multispecific organic anion transporter/MRP genes, primarily 1, 3, 4, 5, and 7, were in fact expressed in these human mesothelioma cell lines as determined by real-time reverse transcription-PCR. These same MRP genes, including, to a lesser extent, MRP-4, were also expressed in pleural mesotheliomas derived from patients as shown by the same methodology. When combined with CDDP or CBCDA, PDX achieved 2-fold greater overall regression of the JMN tumor with a 3-4-fold increase in complete regressions, although some attenuation of dosages of each were required in the combination. These results strongly suggest that PDX has significant potential in the treatment of human pleural mesothelioma, particularly when coadministered with probenecid or combined with platinum compounds.
E-mail classification in the Haystack framework (2003)

This thesis describes the design and implementation of a text classification framework for the Haystack project. As part of this framework, we have built a robust Java API that supports a diverse set of classification algorithms. We have used this framework to build two applications: Cesium, an auto-classification agent for Haystack that is Haystack&amp;apos;s first real autonomous agent, and PorkChop, a spam-filtering plugin for Microsoft Outlook. In order to achieve suitable training and classification speeds, we have augmented the Lucene search engine&amp;apos;s document indexer to compute forward indexes. Finally, unrelated to text classification, we describe the design and implementation of Cholesterol, Haystack&amp;apos;s highly optimized RDF store.
Toxicity of a Biodegradable Microneedle Implant Loaded with Methotrexate as a Sustained Release Device in Normal Rabbit Eye: A Pilot Study (2011)

This sustained release implant containing methotrexate proved to be nontoxic histopathologically and well-tolerated in the eyes of normal rabbit.
Viral Glycoprotein-Mediated Cell Fusion Assays Using Vaccinia Virus Vectors (2004)

The vaccinia virus-based expression of viral envelope glycoprotein genes-derived from enveloped viruses that infect their respective host cells through a pH-independent mechanism of membrane fusion-has been a powerful tool in helping to characterize these important attachment and fusion proteins. The cellular expression of these viral envelope glycoproteins has allowed for the measurement of membrane fusion events using cell-cell fusion or syncytia formation. This method has been enhanced by the addition of a reporter-gene system to the vaccinia virus-based cell-cell fusion assay. This improvement has provided a high-throughput and quantitative aspect to this assay, which can serve as a surrogate for virus entry and is therefore ideally suited in the characterization of numerous enveloped viruses, including biological safety level-4 (BSL-4) agents. This chapter will detail the methods of the vaccinia virus-based reporter-gene fusion assay and how it may be used to characterize the fusion mediated by the BSL-4-classified Hendra and Nipah viruses.
Anticytokinin Activity of N-Phenyl-and N-Pyridylcarbamates (1990)

A new class of non-adenylate anticytokinins, alkyl and phenyl N-phenylcarbamates and related phenyl N-pyridylcarbamates, has been developed. They have a structure that has an immediate resemblance to the non-adenylate class of cytokinins, N ,N′-diphenylureas, and N-pyridyl-N′-phenylureas, and the design of the molecule was made based on insight into the bioisoteric nature between the previous, non-adenylate s-triazine anticytokinins and the carbamate and urea structures. The activity in terms of the I 50 value of the most potent members, 4-fluoro- and 4-chlorophenyl N-(2-chloro-4-pyridyl)carbamates, was 0.3 - 0.5 x 10 -6 M when examined by the tobacco (Nicotiana tabacum L.) callus assay in the presence of 0.05 x 10 -6 M kinetin.