gebhart/patrepeval huggingface dataset:
Purification and characterization of phosphoinositide 3-kinase from rat liver. (1990)

Phosphoinositide 3-kinase was purified 27,000-fold from rat liver. The enzyme was purified by acid precipitation of the cytosol followed by chromatography on DEAE-Sepharose, S-Sepharose, hydroxylapatite, Mono-Q, and Mono-S columns. When analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the purified phosphoinositide 3-kinase preparation contained an 85-kDa protein and a protein doublet of approximately 110 kDa. The 85- and 110-kDa proteins focus together on native isoelectric focusing gels and are cross-linked by dithiobis(succinylamide propionate), showing that the 110- and 85-kDa proteins are a complex. The apparent size of the native enzyme, as determined by gel filtration, is 190 kDa. The 85-kDa subunit is the same protein previously shown to associate with polyoma virus middle T antigen and the platelet-derived growth factor receptor (Kaplan, D. R., Whitman, M., Schaffhausen, B., Pallas, D. C., White, M., Cantley, L., and Roberts, T. M. (1987) Cell 50, 1021-1029). The two proteins co-migrate on two-dimensional gels; and, using a Western blotting procedure, 32P-labeled middle T antigen specifically blots the 85-kDa protein. The purified enzyme phosphorylates phosphatidylinositol, phosphatidylinositol 4-phosphate, and phosphatidylinositol 4,5-bisphosphate. The apparent Km values for ATP were found to be 60 microM with phosphatidylinositol 4-phosphate or phosphatidylinositol 4,5-bisphosphate as the substrate. The apparent Km for phosphatidyinositol is 60 microM, for phosphatidylinositol 4-phosphate is 9 microM, and for phosphatidylinositol 4,5-bisphosphate is 4 microM. The maximum specific activity using phosphatidylinositol as the substrate is 0.8 mumol/mg/min. The enzyme requires Mg2+ with an optimum of 5 mM. Substitution of Mn2+ for Mg2+ results in only approximately 10% of the Mg2(+)-dependent activity. Physiological calcium concentrations have no effect on the enzyme activity. Phosphoinositide 3-kinase has a broad pH optimum around 7.
Non–Small Cell Lung Cancer at the Extremes of Age: Impact on Diagnosis and Treatment (1997)

Age significantly affects the presentation and treatment of non-small cell lung cancer patients. Although thoracic operation imparts the greatest survival advantage, this benefit is diminished due to advanced disease in the younger patients and lack of surgical intervention in the elderly.
Local circuitry of identified projection neurons in cat visual cortex brain slices (1987)

The relationship between pyramidal cell morphology and efferent target was investigated in layer 6 of cat primary visual cortex (area 17). Layer 6 has 2 projections, one to the lateral geniculate nucleus (LGN) and another to the visual claustrum. The cells of origin of each projection were identified by retrograde transport of fluorescent latex microspheres. The labeled cells were visualized in brain slices prepared from area 17, using an epifluorescence compound microscope modified for intracellular recording. Individual retrogradely labeled cells were penetrated and intracellularly stained with Lucifer yellow to visualize the patterns of axons and dendrites associated with each projection. The neurons that give rise to the 2 projections had very different patterns of dendrites and local axonal collaterals, but the patterns within each group were highly stereotyped. The differences between their axonal collaterals were particularly dramatic. Claustrum projecting cells had fine, horizontally directed collaterals that arborized exclusively in layer 6 and lower layer 5. Most LGN projecting cells had virtually no horizontal arborization in layer 6. Instead, they sent widespread collaterals vertically, which arborized extensively in layer 4. The apical dendrites of the 2 groups also differed markedly. Claustrum projecting cells had apical dendrites reaching to layer 1, with branches in layer 5 only, while LGN projecting cells never had an apical dendrite reaching higher than layer 3, with side branches in layers 5 and 4. Therefore, each efferent target must receive inputs from neurons whose synaptic connections within area 17 are significantly different from those of neurons projecting to other targets. This further suggests that distinct visual response properties should be associated with each projection. In addition to the claustrum and LGN projecting cells, about 20% of layer 6 pyramidal neurons lacked an efferent axon. Morphologically, most resembled LGN projecting neurons, but a few had characteristics of claustrum projecting cells. These neurons may represent cells that either failed to make an efferent connection or cells that lost an efferent axon during development. Their frequency suggests that such intrinsic, presumably excitatory, neurons may play a significant role in cortical processing.
Pharmacological Characterization of 30 Human Melanocortin-4 Receptor Polymorphisms with the Endogenous Proopiomelanocortin-Derived Agonists, Synthetic Agonists, and the Endogenous Agouti-Related Protein Antagonist, (2010)

The melanocortin-4 receptor (MC4R) is a G-protein-coupled receptor (GPCR) that is expressed in the central nervous system and has a role in regulating feeding behavior, obesity, energy homeostasis, male erectile response, and blood pressure. Since the report of the MC4R knockout mouse in 1997, the field has been searching for links between this genetic biomarker and human obesity and type 2 diabetes. More then 80 single nucleotide polymorphisms (SNPs) have been identified from human patients, both obese and nonobese controls. Many significant studies have been performed examining the pharmacological characteristics of these hMC4R SNPs in attempts to identify a molecular defects/insights that might link a genetic factor to the obese phenotype observed in patients possessing these mutations. Our laboratory has previously reported the pharmacological characterization of 40 of these polymorphic hMC4 receptors with multiple endogenous and synthetic ligands. The goal of the current study is to perform a similar comprehensive side-by-side characterization of 30 additional human hMC4R with single nucleotide polymorphisms using multiple endogenous agonists [alpha-, beta-, and gamma(2)-melanocyte stimulating hormones (MSH) and adrenocorticotropin (ACTH)], the antagonist agouti-related protein hAGRP(87-132), and synthetic agonists [NDP-MSH, MTII, and the tetrapeptide Ac-His-dPhe-Arg-Trp-NH(2) (JRH887-9)]. These in vitro data, in some cases, provide a putative molecular link between dysfunctional hMC4R's and human obesity. These 30 hMC4R SNPs include R7H, R18H, R18L, S36Y, P48S, V50M, F51L, E61K, I69T, D90N, S94R, G98R, I121T, A154D, Y157S, W174C, G181D, F202L, A219 V, I226T, G231S, G238D, N240S, C271R, S295P, P299L, E308K, I317V, L325F, and 750DelGA. All but the N240S hMC4R were identified in obese patients. Additionally, we have characterized a double I102T/V103I hMC4R. In addition to the pharmacological characterization, the hMC4R variants were evaluated for cell surface expression by flow cytometry. The F51L, I69T, and A219V hMC4Rs possessed full agonist activity and significantly decreased endogenous agonist ligand potency. At the E61K, D90N, Y157S, and C271R hMC4Rs, all agonist ligands examined were only partially efficacious in generating a maximal signaling response (partial agonists) and possessed significantly decreased endogenous agonist ligand potency. Only the A219V, G238D, and S295P hMC4Rs possessed significantly decreased AGRP(87-132) antagonist potency. These data provide new information for use in GPCR computational development as well as insights into MC4R structure ad function.
Heterogeneous nuclear ribonucleoprotein B1 as a new marker of early detection for human lung cancers. (1999)

Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is an RNA binding protein that is required for maturation of mRNA precursor. Tockman et al. previously reported that hnRNP A2/B1 with a M(r) of 31,000 is overexpressed from the early clinical stage of human lung cancer (M. S. Tockman et al., J. Clin. Oncol., 6: 1685-1693, 1988). However, when hnRNP A2/B1 mRNA and hnRNP B1 mRNA were separately studied, we found unique evidence that hnRNP B1 mRNA, which is a splicing variant of hnRNP A2 mRNA, was more significantly elevated in lung cancer tissues than hnRNP A2/B1 mRNA. Our hnRNP B1-specific polyclonal antibody specifically recognized hnRNP B1 protein as a M(r) 37,000 nuclear protein by Western blotting but did not recognize hnRNP A2 protein. Immunohistochemical staining with the hnRNP B1 antibody revealed that hnRNP B1 protein was specifically stained in the nuclei of human cancer cells, and in squamous cell carcinomas in particular, but not in those of normal adjacent lung epithelial cells. We think that hnRNP B1 protein of M(r) 37,000, not hnRNP A2, is well qualified as a biomarker for the detection of human lung cancer.
Next-generation wireless data services: architecture and experience (1999)

Wireless data promises useful services and great convenience. The many technological and economical obstacles that have been hampering its growth are slowly being overcome. In this article we first explain our vision of what next-generation wireless data services may look like. Then we present the different elements of a base architecture designed to support the common requirements and features. As an example, we describe our initial experience in implementing a wireless data server prototype at Bell Laboratories.
Nano hydroxyapatite structures influence early bone formation (2008)

In a study model that aims to evaluate the effect of nanotopography on bone formation, micrometer structures known to alter bone formation, should be removed. Electropolished titanium implants were prepared to obtain a surface topography in the absence of micro structures, thereafter the implants were divided in two groups. The test group was modified with nanosize hydroxyapatite particles; the other group was left uncoated and served as control for the experiment. Topographical evaluation demonstrated increased nanoroughness parameters for the nano-HA implant and higher surface porosity compared to the control implant. The detected features had increased size and diameter equivalent to the nano-HA crystals present in the solution and the relative frequency of the feature size and diameter was very similar. Furthermore, feature density per microm(2) showed a decrease of 13.5% on the nano-HA implant. Chemical characterization revealed calcium and phosphorous ions on the modified implants, whereas the control implants consisted of pure titanium oxide. Histological evaluation demonstrated significantly increased bone formation to the coated (p < 0.05) compared to uncoated implants after 4 weeks of healing. These findings indicate for the first time that early bone formation is dependent on the nanosize hydroxyapatite features, but we are unaware if we see an isolated effect of the chemistry or of the nanotopography or a combination of both.
Effect of Solvent Treatment on Solution-Processed Colloidal PbSe Nanocrystal Infrared Photodetectors (2010)

PbSe colloidal nanocrystals were used to fabricate infrared photodetectors. Low dark currents were obtained by using chemical treatments to improve the nanocrystal film quality and passivate traps in the nanocrystals. The effects of different nanocrystal capping groups, including oleic acid, octylamine, ethanedithiol, and benzenedithiol, on the nanocrystal film quality and the photodiode characteristics were studied. The spectral responsivities and quantum efficiencies of the photodetectors were also measured. We found that the physical quality of the films was very sensitive to the capping groups used for the nanocrystals as well as the specific exchange reactions. Specifically, the dithiol capping groups were found to enhance the rectification of the photodetectors and significantly reduce the dark current in the devices by effectively passivating the surface traps.
Modified dsRNAs that are not processed by Dicer maintain potency and are incorporated into the RISC (2010)

Chemical modification of RNA duplexes can provide practical advantages for RNA interference (RNAi) triggering molecules including increased stability, safety and specificity. The impact of nucleotide modifications on Dicer processing, RISC loading and RNAi-mediated mRNA cleavage was investigated with duplexes >or=25 bp in length. It is known that dsRNAs >or=25 bp are processed by Dicer to create classic 19-bp siRNAs with 3'-end overhangs. We demonstrate that the presence of minimal modification configurations on longer RNA duplexes can block Dicer processing and result in the loading of the full-length guide strand into RISC with resultant mRNA cleavage at a defined site. These longer, modified duplexes can be highly potent gene silencers, with EC50s in the picomolar concentration range, demonstrating that Dicer processing is not required for incorporation into RISC or potent target silencing.
A prodrug approach to the design of cRaf1 kinase inhibitors with improved cellular activity. (2001)

Earlier we reported potent cRaf1 kinase inhibitors with a key acidic phenol pharmacophore that had, at best, adequate cellular efficacy. To improve the cellular potency, phenol isosteres and prodrugs were investigated. Many phenol isosteres were synthesized and tested, but failed to provide adequate enzyme potency. A prodrug approach resulted in a 2- to 17-fold improvement over the parent compound in cell-based efficacy.
Phase 1 and pharmacokinetic study of bolus-infusion flavopiridol followed by cytosine arabinoside and mitoxantrone for acute leukemias (2011)

Flavopiridol is a protein bound, cytotoxic, cyclin-dependent kinase inhibitor. Flavopiridol given by 1-hour bolus at 50 mg/m(2) daily 3 times followed by cytosine arabinoside and mitoxantrone (FLAM) is active in adults with poor-risk acute leukemias. A pharmacologically derived "hybrid" schedule (30-minute bolus followed by 4-hour infusion) of flavopiridol was more effective than bolus administration in refractory chronic lymphocytic leukemia. Our phase 1 trial "hybrid FLAM" in 55 adults with relapsed/refractory acute leukemias began at a total flavopiridol dose of 50 mg/m(2) per day 3 times (20-mg/m(2) bolus, 30-mg/m(2) infusion). Dose-limiting toxicity occurred at level 6 (30-mg/m(2) bolus, 70-mg/m(2) infusion) with tumor lysis, hyperbilirubinemia, and mucositis. Death occurred in 5 patients (9%). Complete remission occurred in 22 (40%) across all doses. Overall and disease-free survivals for complete remission patients are more than 60% at more than 2 years. Pharmacokinetics demonstrated a dose-response for total and unbound plasma flavopiridol unrelated to total protein, albumin, peripheral blast count, or toxicity. Pharmacodynamically, flavopiridol inhibited mRNAs of multiple cell cycle regulators, but with uniform increases in bcl-2. "Hybrid FLAM" is active in relapsed/refractory acute leukemias, with a recommended "hybrid" dose of bolus 30 mg/m(2) followed by infusion of 60 mg/m(2) daily for 3 days. This clinical trial is registered at www.clinicaltrials.gov as #NCT00470197.
Detecting Anomalous Trajectories Using the Dempster-Shafer Evidence Theory Considering Trajectory Features from Taxi GNSS Data (2018)

In road networks, an ‘optimal’ trajectory is a geometrically optimal drive from the source point to the destination point. In reality, the driver’s driving experience or road traffic conditions will lead to differences between the ‘actual’ trajectory and the ‘optimal’ trajectory. When the differences are excessive, these trajectories are considered as anomalous trajectories. In addition, these differences can be observed in various trajectory features, such as velocity, distance, turns, and intersections. In this paper, our aim is to fuse these trajectory features and to quantitatively describe this difference to infer anomalous trajectories. The Dempster-Shafer (D-S) evidence theory is a theory and method that uses different features as evidence to infer uncertainty. The theory does not require prior knowledge or conditional probabilities. Therefore, we propose an automatic, anomalous trajectory inference method based on the D-S evidence theory that considers driving behavior and road network constraints. To achieve this objective, we first obtain all of the ‘actual’ trajectories of drivers for different source-destination pairs in taxi Global Navigation Satellite System (GNSS) trajectories. Second, we define and extract five trajectory features: route selection ( R S ), intersection rate ( I R ), heading change rate ( HCR ) , slow point rate ( SPR ), and velocity change rate ( VCR ) . Then, different features of each trajectory are combined as evidence according to Dempster’s combinational rule. The precise probability interval of each trajectory is calculated based on the D-S evidence theory. Finally, we obtain the anomalous possibility of all real trajectories and infer anomalous trajectories whose trajectory features are significantly different from normal ones. The experimental results show that the proposed method can infer anomalous trajectories effectively and that it can be used to monitor driver behavior automatically and to discover adverse urban traffic events.
Simultaneous Fault Detection and Identification for Plasma Etching Processes (2002)

State-of-the-art plasma processes are often pushed to the limits of the current technology, resulting in processes that have little or no margin for error. Increasingly, there is a need for fast, accurate, and sensitive detection and identification of equipment and process faults to maintain high process yields in manufacturing. In this work, we present an approach that simultaneously combines fault detection and classification together. Our algorithm uses linear discriminant analysis [1] methods to train for specific kinds of faults, e.g. a leaky mass flow controller. We can then monitor a small number of fault detection control charts, which are expressly set up to determine whether a specific fault has occurred or not. It can be shown that this approach provides higher sensitivity to specific kinds of faults than other multivariate approaches such as T, while detecting and classifying them simultaneously. We will review an example set of data and describe the performance of the new approach and compare it to other multivariate approaches. This work is an extension of the multivariate endpoint detection approach that will be discussed in another talk at this symposium, based on [2].
Winter Survival of Individual Honey Bees and Honey Bee Colonies Depends on Level of Varroa destructor Infestation (2012)

Background: Recent elevated winter loss of honey bee colonies is a major concern. The presence of the mite Varroa destructor in colonies places an important pressure on bee health. V. destructor shortens the lifespan of individual bees, while long lifespan during winter is a primary requirement to survive until the next spring. We investigated in two subsequent years the effects of different levels of V. destructor infestation during the transition from short-lived summer bees to long-lived winter bees on the lifespan of individual bees and the survival of bee colonies during winter. Colonies treated earlier in the season to reduce V. destructor infestation during the development of winter bees were expected to have longer bee lifespan and higher colony survival after winter.
Functional Interactions between Tumor and Peripheral Nerve: Changes in Excitability and Morphology of Primary Afferent Fibers in a Murine Model of Cancer Pain (2001)

We used a murine model to investigate functional interactions between tumors and peripheral nerves that may contribute to pain associated with cancer. Implantation of fibrosarcoma cells in and around the calcaneus bone produced mechanical hyperalgesia of the ipsilateral paw. Electrophysiological recordings from primary afferent fibers in control and hyperalgesic mice with tumor revealed the development of spontaneous activity (0.2-3.4 Hz) in 34% of cutaneous C-fibers adjacent to the tumor (9-17 d after implantation). C-fibers in tumor-bearing mice exhibited a mean decrease in heat threshold of 3.5 +/- 0.10 degrees C. We also examined innervation of the skin overlying the tumor. Epidermal nerve fibers (ENFs) were immunostained for protein gene product 9.5, imaged using confocal microscopy, and analyzed in terms of number of fibers per millimeter of epidermal length and branching (number of nodes per fiber). Divergent morphological changes were linked to tumor progression. Although branching of ENFs increased significantly relative to control values, in later stages (16-24 d after implantation) of tumor growth a sharp decrease in the number of ENFs was observed. This decay of epidermal innervation of skin over the tumor coincided temporally with gradual loss of electrophysiological activity in tumor-bearing mice. The development of spontaneous activity and sensitization to heat in C-fibers and increased innervation of cutaneous structures within the first 2 weeks of tumor growth suggest activation and sensitization of a proportion of C-fibers. The decrease in the number of ENFs observed in later stages of tumor development implicates neuropathic involvement in this model of cancer pain.
Preclinical Evaluation of Adult Stem Cell Engraftment and Toxicity in the CNS of Rhesus Macaques (2006)

Congenital neurodegenerative diseases exhibit progressive postnatal neurologic impairment leading to premature death and are intractable to systemic therapies such as bone marrow transplantation. We injected bone marrow-derived mesenchymal stem cells (MSCs) into the CNS of young adult rhesus macaques to evaluate their safety and feasibility as vectors for direct intervention of neurologic disorders. Levels of engrafted male, donor MSCs were quantified in the CNS of female transplant recipients by real-time PCR using an SRY gene-specific probe. Analysis of coronal brain slices encompassing one-third of the total brain volume revealed engraftment levels ranging from 0.026 x 10(-3) to 0.163 x 10(-3)% of the total DNA content of brain tissue. Fine-mapping revealed male DNA distributed within specific anatomic structures along the neuraxis where label-retaining MSCs were visualized in histological sections by immunohistochemistry. Double labeling of sections confirmed that engrafted donor cells lacked expression of the macrophage marker CD68, the astrocytes marker GFAP, and neuronal markers NeuN and MAP2. MSC engraftment had no adverse effects on animal health, behavior, postural and locomotor patterns, or upper limb motor performance evaluated over a 6-month period posttransplantation. Therefore, MSC-based therapies represent a safe alternative for clinical intervention of CNS disorders.