gebhart/patrepeval huggingface dataset:
Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors. (2003)

Cytotoxic chemotherapy is generally considered immunosuppressive, with neutropenia and lymphopenia being common adverse side effects. In this context, we have shown previously that the cytidine analogue, gemcitabine, abolishes humoral responses but, in contrast, augments antigen-specific cellular antitumor immunity. This augmentation occurs in the context of increased antigen cross-presentation, T lymphocyte expansion, and infiltration of the tumor. Here, we combine an immunotherapy (CD40 ligation using FGK45; 100 micro g; i.p., q2dx3) with gemcitabine (120 microg/gram; i.p.; q3dx5) to treat established solid tumors. This protocol induced long-term cures in < or =80% of mice, and all of the cured mice were resistant to tumor rechallenge. Synergy between the drug and immunotherapy could not be established in vitro and was only seen in the context of tumor cell death. It was associated with an increase in both CD4 and CD8 T-cell infiltration of the tumor, but depletion studies clearly showed that CD4 T cells were not a necessary component of the cure. In contrast, CD8 T cells were absolutely required for the success of this treatment regimen. The priming effect of gemcitabine was not limited to debulking, because mice resected to an equivalent, or lesser residual tumor volume did not eradicate tumor with subsequent immunotherapy. This study provides evidence that chemotherapy has the capacity to augment cellular antitumor immunity, a finding with wider implications for the management of treatment-resistant solid tumors.
A Brief History of IL-9 (2011)

IL-9 was first described in the late 1980s as a member of a growing number of cytokines that had pleiotropic functions in the immune system. Although many biological functions have been attributed to IL-9, it remains an understudied cytokine. A resurgence of interest in IL-9 has been spurred by recent work demonstrating a role for IL-9 in regulating inflammatory immunity and defining the transcription factors that activate the Il9 gene in cells that most efficiently produce IL-9. In this review, we summarize the characterization of IL-9 biological activities, highlight roles for the cytokine that are clearly defined, and outline questions regarding IL-9 functions that still require further exploration.
Genomic plasticity of the causative agent of melioidosis, Burkholderia pseudomallei (2004)

Burkholderia pseudomallei is a recognized biothreat agent and the causative agent of melioidosis. This Gram-negative bacterium exists as a soil saprophyte in melioidosis-endemic areas of the world and accounts for 20% of community-acquired septicaemias in northeastern Thailand where half of those affected die. Here we report the complete genome of B. pseudomallei, which is composed of two chromosomes of 4.07 megabase pairs and 3.17 megabase pairs, showing significant functional partitioning of genes between them. The large chromosome encodes many of the core functions associated with central metabolism and cell growth, whereas the small chromosome carries more accessory functions associated with adaptation and survival in different niches. Genomic comparisons with closely and more distantly related bacteria revealed a greater level of gene order conservation and a greater number of orthologous genes on the large chromosome, suggesting that the two replicons have distinct evolutionary origins. A striking feature of the genome was the presence of 16 genomic islands (GIs) that together made up 6.1% of the genome. Further analysis revealed these islands to be variably present in a collection of invasive and soil isolates but entirely absent from the clonally related organism B. mallei. We propose that variable horizontal gene acquisition by B. pseudomallei is an important feature of recent genetic evolution and that this has resulted in a genetically diverse pathogenic species.
국내 항공여행시장 세분화를 통한 항공여객 욕구분석 및 마케팅전략 (2009)

본 연구는 국내 항공여행시장의 비즈니스 환경 및 고객 욕구 변화에 따라 시장을 재조명하고자 시장세분화를 실시하였다. 그 결과 비교적 안정적이고 의미 있는 세 개 세분시장이 도출되었으며, 본질적으로 제반서비스, 안전성, 경제성에 집중되었다. 선택속성에 대한 세분시장의 동질성은 선택행동에 대하여 유의한 예측력을 가지며, 프로파일의 결과는 항공사 서비스 상품 특성화를 위한 세 가지 잠재적인 전략을 밝히고 있다. 또한 전통적으로 항공여행시장의 세분화에 주로 사용되어 온 선험적 기준들이 세분시장에서 유용한 의미를 가지는지를 평가한 결과, 인구통계적 지표들은 세분시장 간에 비교적 적은 차이를 보인 반면, 여행특성들은 모두 통계적으로 유의한 차이가 발견되었다. 특히 여행목적에 따른 여행객들의 욕구 및 항공사 선호도를 평가한 결과, 현재 항공사들에 의해 적용되고 있는 세분화가 고객들의 선호도 패턴을 적절하게 반영하지 못하고 있음을 확인하였다. 결과적으로 본 연구는 최근 문헌들에서 제기되고 있는 항공 여행객들의 욕구 및 믹스의 변화를 지지하고, 전통적인 시장세분화에 대한 비효율성을 입증함으로써 연구의 학문적, 실무적 의의를 가진다.
A Day in the Life of PubMed: Analysis of a Typical Day's Query Log (2007)

PubMed's usage profile should be considered when educating users, building user interfaces, and developing future biomedical information retrieval systems.
Distributed interleaving of paralleled power converters (1997)

This paper introduces a distributed approach to interleaving paralleled power converter cells. Unlike conventional methods, the distributed approach requires no centralized control, automatically accommodates varying numbers of converter cells, and is highly tolerant of subsystem failures. A general methodology for achieving distributed interleaving is proposed, along with a specific implementation approach. The design and experimental verification of a 50 kHz prototype system is presented, and quantitative performance comparisons are made between synchronized clocking, independent clocking, and interleaved clocking of the converter cells. The experimental results corroborate the analytical predictions and demonstrate the tremendous benefits of the distributed interleaving approach.
Stochastic Rank-1 Bandits (2016)

We propose stochastic rank-$1$ bandits, a class of online learning problems where at each step a learning agent chooses a pair of row and column arms, and receives the product of their values as a reward. The main challenge of the problem is that the individual values of the row and column are unobserved. We assume that these values are stochastic and drawn independently. We propose a computationally-efficient algorithm for solving our problem, which we call Rank1Elim. We derive a $O((K + L) (1 / Δ) \log n)$ upper bound on its $n$-step regret, where $K$ is the number of rows, $L$ is the number of columns, and $Δ$ is the minimum of the row and column gaps; under the assumption that the mean row and column rewards are bounded away from zero. To the best of our knowledge, we present the first bandit algorithm that finds the maximum entry of a rank-$1$ matrix whose regret is linear in $K + L$, $1 / Δ$, and $\log n$. We also derive a nearly matching lower bound. Finally, we evaluate Rank1Elim empirically on multiple problems. We observe that it leverages the structure of our problems and can learn near-optimal solutions even if our modeling assumptions are mildly violated.
Incubated Protein Reduction and Digestion on an Electrowetting-on-Dielectric Digital Microfluidic Chip for MALDI-MS (2010)

Localized heating of droplets on an electrowetting-on-dielectric (EWOD) chip has been implemented and shown to accelerate trypsin digestion reaction rates, sample drying, and matrix crystallization for matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). Achieving this involved extending the functionality of previous EWOD droplet-based techniques by developing a multifunctional electrode with closed-loop temperature control, while minimizing overall system complexity and addressing challenges associated with rapid evaporation. For the EWOD chip design, we discuss the performance of multifunctional surface electrodes for actuation, localized Joule heating, and thermistic temperature sensing. Furthermore, a hydrophilic pattern is formed in the multifunctional electrode to control the location of an evaporating droplet on the electrode. To demonstrate the capabilities and limitations of this technique, we performed three experiments and measured the results using MALDI-MS: (i) insulin disulfide reductions in dithiothreitol (DTT) over a range of heater temperatures (22-70 °C) to show how reaction rates can be affected by thermal control, (ii) insulin disulfide reductions at 130 °C in dimethyl sulfoxide (DMSO) to demonstrate a reaction in a high boiling point solvent, and (iii) tryptic digestions of cytochrome c at 22 and 40 °C to show that heated droplets can yield reasonably higher peptide sequence coverage than unheated droplets. Although they do not decouple the effects of changing temperatures and concentrations, these experiments verified that thermal cycling by EWOD electrodes accelerates reaction rates in liquid droplets in air.
The Proangiogenic Action of Thyroid Hormone Analogue GC-1 Is Initiated at an Integrin: [RETRACTED] (2005)

Our early reported investigations have demonstrated potent proangiogenic effects of L-thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3) in the chick chorioallantoic membrane (CAM) model. Tetraiodothyroacetic acid (tetrac) blocks T4 binding to plasma membranes and its pro-angiogenic effect. T4/T3 stimulates expression of fibroblast growth factor 2 (FGF2) in endothelial cells. Thyroid hormone (T4/T3) is principally responsible for transcriptional activation mediated by nuclear thyroid hormone receptors TRbeta and TRalpha. In contrast, the hormone analogue GC-1 also stimulates transcriptional activation via TRbeta1. In the present study, we have defined the effect of GC-1, compared with T4 and T4-agarose, on angiogenesis in the CAM assay. GC-1 demonstrated a proangiogenic effect similar to that of T4 and T4-agarose. Tetrac inhibited GC-1- and T4-induced angiogenesis, indicating dependence on T4 and GC-1 binding to plasma membranes. The effects of GC-1, T4-agarose, and FGF2 were blocked by PD 98059, a mitogen-activated protein kinase (MAPK) pathway inhibitor. Additionally, the alphavbeta3 integrin antagonist XT199 inhibited angiogenesis induced by T4-agarose, GC-1, or FGF2. Thus, the proangiogenic effects of GC-1 and T4 are initiated at the plasma membrane, require interaction with alphavbeta3 integrin receptor, and are dependent on MAPK activation.
Fundamentals and application of magnetic particles in cell isolation and enrichment: a review (2014)

Magnetic sorting using magnetic beads has become a routine methodology for the separation of key cell populations from biological suspensions. Due to the inherent ability of magnets to provide forces at a distance, magnetic cell manipulation is now a standardized process step in numerous processes in tissue engineering, medicine, and in fundamental biological research. Herein we review the current status of magnetic particles to enable isolation and separation of cells, with a strong focus on the fundamental governing physical phenomena, properties and syntheses of magnetic particles and on current applications of magnet-based cell separation in laboratory and clinical settings. We highlight the contribution of cell separation to biomedical research and medicine and detail modern cell-separation methods (both magnetic and non-magnetic). In addition to a review of the current state-of-the-art in magnet-based cell sorting, we discuss current challenges and available opportunities for further research, development and commercialization of magnetic particle-based cell-separation systems.
Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial (2002)

Mildly thrombocytopenic patients with relapsed or refractory low-grade non-Hodgkin lymphoma (NHL) have an increased risk of chemotherapy-induced myelosuppression following treatment. The safety and efficacy of radioimmunotherapy with a reduced dose of (90)Y ibritumomab tiuxetan (0.3 mCi/kg [11 MBq/kg]; maximum 32 mCi [1.2 GBq]) was evaluated in 30 patients with mild thrombocytopenia (100-149 x 10(9) platelets/L) who had advanced, relapsed or refractory, low-grade, follicular, or transformed B-cell NHL. The ibritumomab tiuxetan regimen included an infusion of rituximab (250 mg/m(2)) and injection of (111)In ibritumomab tiuxetan (5 mCi [185 MBq]) for dosimetry evaluation, followed 1 week later with rituximab (250 mg/m(2)) and (90)Y ibritumomab tiuxetan (0.3 mCi/kg [11 MBq/kg]). Patients (median age, 61 years; 90% stage III/IV at study entry; 83% follicular lymphoma; and 67% with bone marrow involvement) had a median of 2 prior therapy regimens (range, 1-9). Estimated radiation-absorbed doses were well below the study-defined maximum allowable for all 30 patients. With the use of the International Workshop criteria for NHL response assessment, the overall response rate was 83% (37% complete response, 6.7% complete response unconfirmed, and 40% partial response). Kaplan-Meier estimated median time to progression (TTP) was 9.4 months (range, 1.7-24.6). In responders, Kaplan-Meier estimated median TTP was 12.6 months (range, 4.9-24.6), with 35% of data censored. Toxicity was primarily hematologic, transient, and reversible. The incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 33%, 13%, and 3%, respectively. Reduced-dose ibritumomab tiuxetan is safe and well tolerated and has significant clinical activity in this patient population.
In vitro and in vivo neuroprotective activity of the cardiac glycoside oleandrin from Nerium oleander in brain slice‐based stroke models (2011)

The principal active constituent of the botanical drug candidate PBI-05204, a supercritical CO(2) extract of Nerium oleander, is the cardiac glycoside oleandrin. PBI-05204 shows potent anticancer activity and is currently in phase I clinical trial as a treatment for patients with solid tumors. We have previously shown that neriifolin, which is structurally related to oleandrin, provides robust neuroprotection in brain slice and whole animal models of ischemic injury. However, neriifolin itself is not a suitable drug development candidate and the FDA-approved cardiac glycoside digoxin does not cross the blood-brain barrier. We report here that both oleandrin as well as the full PBI-05204 extract can also provide significant neuroprotection to neural tissues damaged by oxygen and glucose deprivation as occurs in ischemic stroke. Critically, we show that the neuroprotective activity of PBI-05204 is maintained for several hours of delay of administration after oxygen and glucose deprivation treatment. We provide evidence that the neuroprotective activity of PBI-05204 is mediated through oleandrin and/or other cardiac glycoside constituents, but that additional, non-cardiac glycoside components of PBI-05204 may also contribute to the observed neuroprotective activity. Finally, we show directly that both oleandrin and the protective activity of PBI-05204 are blood brain barrier penetrant in a novel model for in vivo neuroprotection. Together, these findings suggest clinical potential for PBI-05204 in the treatment of ischemic stroke and prevention of associated neuronal death.
Quality factors in micron- and submicron-thick cantilevers (2000)

Micromechanical cantilevers are commonly used for detection of small forces in microelectromechanical sensors (e.g., accelerometers) and in scientific instruments (e.g., atomic force microscopes). A fundamental limit to the detection of small forces is imposed by thermomechanical noise, the mechanical analog of Johnson noise, which is governed by dissipation of mechanical energy. This paper reports on measurements of the mechanical quality factor Q for arrays of silicon-nitride, polysilicon, and single-crystal silicon cantilevers. By studying the dependence of Q on cantilever material, geometry, and surface treatments, significant insight into dissipation mechanisms has been obtained. For submicron-thick cantilevers, Q is found to decrease with decreasing cantilever thickness, indicating surface loss mechanisms. For single-crystal silicon cantilevers, significant increase in room temperature Q is obtained after 700/spl deg/C heat treatment in either N/sub 2/ Or forming gas. At low temperatures, silicon cantilevers exhibit a minimum in Q at approximately 135 K, possibly due to a surface-related relaxation process. Thermoelastic dissipation is not a factor for submicron-thick cantilevers, but is shown to be significant for silicon-nitride cantilevers as thin as 2.3 /spl mu/m.
TGF-β switches from tumor suppressor to prometastatic factor in a model of breast cancer progression (2003)

The TGF-β signaling network plays a complex role in carcinogenesis because it has the potential to act as either a tumor suppressor or a pro-oncogenic pathway. Currently, it is not known whether TGF-β can switch from tumor suppressor to pro-oncogenic factor during the course of carcinogenic progression in a single cell lineage with a defined initiating oncogenic event or whether the specific nature of the response is determined by cell type and molecular etiology. To address this question, we have introduced a dominant negative type II TGF-β receptor into a series of genetically related human breast–derived cell lines representing different stages in the progression process. We show that decreased TGF-β responsiveness alone cannot initiate tumorigenesis but that it can cooperate with an initiating oncogenic lesion to make a premalignant breast cell tumorigenic and a low-grade tumorigenic cell line histologically and proliferatively more aggressive. In a high-grade tumorigenic cell line, however, reduced TGF-β responsiveness has no effect on primary tumorigenesis but significantly decreases metastasis. Our results demonstrate a causal role for loss of TGF-β responsiveness in promoting breast cancer progression up to the stage of advanced, histologically aggressive, but nonmetastatic disease and suggest that at that point TGF-β switches from tumor suppressor to prometastatic factor.
Angiopathic consequences of saturating the plasma scavenger system for actin. (1990)

Two plasma proteins, vitamin D-binding protein (actin monomer sequestrant) and gelsolin (actin polymer severing), have been found in association with actin in plasma from ill humans and during experimental injury. In vitro, these are the only plasma proteins that display a high affinity for actin. We infused increasing amounts of globular actin intravenously to rats to evaluate its disposition in plasma and tissues. Intravascular filament formation, microthrombi, and endothelial injury were observed, especially in the pulmonary circulation. These pathological changes were not observed when the globular actin in the infusate had been preincubated with the vitamin D-binding protein in vitro. Complexes of actin with both proteins were found in the plasma, suggesting a saturable, plasma actin-binding system in vivo. Our findings suggest that in vivo saturation of these proteins' actin-binding capacities may serve as a paradigm for pulmonary vascular disorders seen during widespread tissue trauma and cell lysis.
Nanotechnology Applications in Viscoelastic Surfactant Stimulation Fluids (2008)

Summary Viscoelastic surfactant (VES) fluids have been used widely in the oil industry as completion and stimulation fluids. The surfactants arrange structurally to form rod-like micelles that increase VES-fluid viscosity for regular fracturing and fracture-packing fluids. However, high fluid leakoff and low viscosities at elevated temperatures have limited VES fluids to hydraulic fracturing and fracture-packing applications. This paper will introduce a nanotechnology application for maintaining viscosity at high temperatures and controlling the loss of VES fluid without generating formation damage. The nanoparticles studied are 35-nm inorganic crystals that display unique surface morphology and surface reactivity. These nanometer-scale particles associate with VES micelles through chemisorption and surface-charge attraction to stabilize fluid viscosity at high temperatures and to produce a pseudofilter cake of viscous VES fluid that reduces significantly the rate of fluid loss and improves fluid efficiency. When internal breakers are used to break the VES micelles, the fluid will lose its viscosity dramatically and the pseudofilter cake will then break into brine and nanoparticles. Because the particles are small enough to pass through the pore throat of producing formations, they will be flowed back with the producing fluids, and no damage will be generated. The results of rheology, leakoff, and core-flow tests will be presented for the VES-fluid systems at temperatures 150 and 250°F.
Matrix metalloprotease-9 dysregulation in lower airway secretions of cystic fibrosis patients (2007)

Matrix metalloproteases (MMPs) are proteolytic enzymes that regulate extracellular matrix turnover and aid in restoring tissue architecture following injury. There is an emerging role for extracellular matrix destruction in the pathogenesis of chronic neutrophilic lung diseases. In this study, we examined the expression and activity profiles of MMPs in lower airway secretions from cystic fibrosis (CF) patients, patients with acute respiratory failure (ARF), and normal controls. A discrete repertoire of MMP isoforms was found in the CF samples, with robust MMP-9 expression compared with normal controls and ARF. CF samples possessed increased levels of active MMP-9, as well as decreased amounts of tissue inhibitor of metalloprotease-1 (TIMP-1), a natural inhibitor of MMP-9. The CF inpatient samples demonstrated fully active MMP-9 activity compared with CF outpatients, ARF, and normal controls. CF samples also demonstrated increased human neutrophil elastase (HNE) levels compared with ARF and normal controls. To examine potential mechanisms for the protease dysregulation seen in the CF clinical samples, in vitro studies demonstrated that HNE could activate pro-MMP-9 and also degrade TIMP-1; this HNE-based activation, however, was not seen with MMP-8. A strong correlation was seen between HNE and MMP-9 activity in CF inpatient samples. Finally, the dysregulated MMP-9 activity seen in CF inpatient sputum samples could be significantly reduced by the use of MMP-9 inhibitors. Collectively, these findings further emphasize the proposed protease/antiprotease imbalance in chronic neutrophilic lung disease, providing a potential mechanism contributing to this proteolytic dysregulation.
Range-only underwater target localization: Path characterization (2016)

Underwater localization using acoustic signals is one of the main components in a navigation system for an AUV as a more accurate alternative to dead-reckoning techniques. While different methods based on the idea of multiple beacons have been studied, other approaches use only one beacon, which reduces the system costs and deployment complexity. The inverse approach for single-beacon navigation is to use this method for target localization by an underwater or surface vehicle. In this paper we present a method of range-only target localization using a Wave Glider <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">™</sup> , for which simulations and sea tests have been conducted to determine optimal parameters to minimize acoustic energy use and search time and to maximize location accuracy and precision.
An Architecture for A Camputs-Scale Wireless Mobile Internet (1995)

This paper proposes a network architecture to support mobile communication in a large university campus.The design allows each mobile host to maintain network connectivity while roaming freely in the campus.Called Crosspoint, the design combines wireless local-area network (LAN) technology with high-speed Asynchronous Transfer Mode (A1M) switching technology.The combination provides a wireless communication system with sufficient aggregate bandwidth to handle massive, synchronized movements of mobile hosts.Furthermore, the design requires no modification to conventional network software on mobile hosts, stationary hosts, or existing IP routers.We have implemented a prototype of the Crosspoint design.This paper also describes the basic protocols used in the implementation.