gebhart/patrepeval huggingface dataset:
Treatment with IL2/Vaccinia Recombinant Virus Leads to Serologic, Histologic and Phenotypic Normalization of Autoimmune MRL/lpr-lpr Mice (1991)

We have analyzed the effect of IL2 administered in vivo on both the lymphoproliferation and autoimmune disease progression of MRL/lpr mice. Human IL2 was delivered by infecting MRL/lpr mice with vaccinia virus recombinants at different stages of lpr disease. The results reported here showed that treatment of lpr mice with IL2 mediated: (1) restored normal thymic differentiation illustrated by an expansion of the double positive population accompanied by increased numbers of mature thymocytes; (2) depletion of the peripheral CD3+ CD4- CD8- (DN) T-cell population; (3) normalization in the pattern of TcRV beta gene expression displayed by mature T cells; (4) decreased urine-protein levels and immune complex deposition in the kidney, with a resultant absence of glomerulonephritis; and (5) an increased longevity (from 195 to more than 400 days). We speculate that the dramatic reduction in the abnormally expanded CD3+ DN T-cell population following IL2 therapy might be directly related to the amelioration and/or prevention of autoimmune disease in these mice. Collectively, these results suggest that diseases showing a selective expansion of DN cells should be envisaged as possible targets for the treatment described here.
A Novel Technique for-the Design of High Efficiency Power Amplifiers (1994)

A novel technique for the design of highly efficient power amplifiers based on an understanding of large signal device behavior has been developed. This is intrinsically a linear circuit analysis procedure employing the concept of conversion matrices. This technique represents a numerically efficient method of analyzing design trade-offs in topology and element values. An extremely small (18mm2) amplifier was designed using this technique and yielded 62% PAE at 1.5 W output power.
Nanoscale electro-optic modulators based on graphene-slot waveguides (2012)

Research on graphene has revealed its remarkable electro-optic properties, which promise to satisfy the needs of future electro-optic modulators. However, its ultrasmall thickness, compared with operating light wavelength, downplays its role in an optoelectronic device. The key to achieve efficient electro-optic modulation based on graphene is to enhance its interaction with light. To this end, some novel waveguides and platforms will be employed to enhance the interaction. Herein, we present our recent exploration of graphene electro-optic modulators based on graphene sandwiched in dielectric or plasmonic waveguides. With a suitable gate voltage, the dielectric constant of graphene can be tuned to be very small due to the effect of intraband electronic transition, resulting in &#x201C;graphene-slot waveguides&#x201D; and greatly enhanced absorption modes. Up to 3 dB modulation depth can be achieved within 800&#xA0;nm long silicon waveguides, or 120&#xA0;nm long plasmonic waveguides based on three-dimensional numerical simulations. They have the advantages of nanoscale footprints, small insertion loss, low power consumption, and potentially ultrahigh speed, as well as being CMOS-compatible.
Environment-Induced Degradation and Crack-Growth Studies of Candidate Target Materials: AAA Task-4 Quarterly (September 1 – November 30, 2001) Report (2001)

The primary objective of this task is to evaluate the effect of hydrogen on environment-assisted cracking of candidate materials for applications in spallation-neutron-target (SNT) systems such as accelerator production of tritium (APT) and accelerator transmutation of waste (ATW). The materials selected for evaluation and characterization are martensitic stainless steels including HT- 9, EP 823 and 422. The susceptibility to stress corrosion cracking (SCC) and hydrogen embrittlement (HE) of these alloys will be evaluated in environments of interest using tensile specimens under constant load and slow-strain-rate (SSR) conditions. The extent and morphology of cracking of these alloys will further be evaluated by optical microscopy and scanning electron microscopy (SEM). The concentration of hydrogen resulting from cathodic charging will be analyzed by secondary ion mass spectrometry (SIMS).
Expansion of Cytomegalovirus pp65 and IE-1 Specific Cytotoxic T Lymphocytes for Cytomegalovirus-Specific Immunotherapy Following Allogeneic Stem Cell Transplantation (2008)

Adoptive immunotherapy with antigen-specific cytotoxic T lymphocytes (CTLs) has proven effective in restoring cellular immunity to cytomegalovirus (CMV) and preventing viral reactivation after allogeneic stem cell transplantation (SCT). In an effort to develop a cost-effective, relatively rapid method of CMV CTL expansion, we investigated the use of a pool of overlapping CMV peptides. Because the possibility exists of vaccinating CMV-seronegative donors, and these individuals may have T cell responses predominantly against IE-1, commercially available peptide mixes for pp65 as well as IE-1 were used to stimulate CTLs from 10 seropositive donors. Of these 10 donors, 4 responded to pp65 only, 1 did not respond to either pp65 or IE-1, 4 responded to both pp65 and IE-1, and 1 responded to IE-1 only. These CMV- specific T cells included a mixture of CD4(+) and CD8(+) effectors, and specific cytotoxicity correlated with interferon-gamma production. The costs associated with a 28-day maintenance course of intravenous ganciclovir, cidofovir, foscarnet, and valganciclovir, as well as the preparation and shipping a single dose of CTLs, were determined. The price of generating CMV CTLs using this method was comparable to or less expensive than a 28-day maintenance course for these agents, not including the costs associated with drug administration, supportive care, and the treatment of drug-related complications. Considering the relative ease, low cost, and the fact that CTL administration can result in CMV-specific immune reconstitution, this option should be considered for patients with CMV reactivation or for prophylaxis in patients at high risk for infection.
Electric-pulse-induced reversible resistance change effect in magnetoresistive films (2000)

A large electric-pulse-induced reversible resistance change active at room temperature and under zero magnetic field has been discovered in colossal magnetoresistive (CMR) Pr0.7Ca0.3MnO3 thin films. Electric field-direction-dependent resistance changes of more than 1700% were observed under applied pulses of ∼100 ns duration and as low as ±5 V magnitude. The resistance changes were cumulative with pulse number, were reversible and nonvolatile. This electrically induced effect, observed in CMR materials at room temperature has both the benefit of a discovery in materials properties and the promise of applications for thin film manganites in the electronics arena including high-density nonvolatile memory.
Metformin Does Not Affect Cancer Risk: A Cohort Study in the U.K. Clinical Practice Research Datalink Analyzed Like an Intention-to-Treat Trial (2014)

In this large study, individuals with diabetes who used metformin had a similar risk of developing cancer compared with those who used sulfonylureas.
Grassmannian beamforming for multiple-input multiple-output wireless systems (2004)

Multiple-input multiple-output (MIMO) wireless systems provides capacity much larger than that provided by traditional single-input single-output (SISO) wireless systems. Beamforming is a low complexity technique that increases the receive signal-to-noise ratio (SNR), however, it requires channel knowledge. Since in practice channel knowledge at the transmitter is difficult to realize, we propose a technique where the receiver designs the beamforming vector and sends it to the transmitter by transmitting a label in a finite set, or codebook, of beamforming vectors. A codebook design method for quantized versions of maximum ratio transmission, equal gain transmission, and generalized selection diversity with maximum ratio combining at the receiver is presented. The codebook design criterion exploits the quantization problem's relationship with Grassmannian line packing. Systems using the beamforming codebooks are shown to have a diversity order of the product of the number of transmit and the number of receive antennas. Monte Carlo simulations compare the performance of systems using this new codebook method with the performance of systems using previously proposed quantized and unquantized systems.
Heterogeneous conditions in dissolved oxygen affect N‐glycosylation but not productivity of a monoclonal antibody in hybridoma cultures (2004)

It is known that heterogeneous conditions exist in large-scale animal cell cultures. However, little is known about how heterogeneities affect cells, productivities, and product quality. To study the effect of non-constant dissolved oxygen tension (DOT), hybridomas were subjected to sinusoidal DOT oscillations in a one-compartment scale-down simulator. Oscillations were forced by manipulating the inlet oxygen partial pressure through a feedback control algorithm in a 220-mL bioreactor maintained at a constant agitation. Such temporal DOT oscillations simulate spatial DOT gradients that can occur in large scales. Different oscillation periods, in the range of 800 to 12,800 s (axis of 7% (air saturation) and amplitude of 7%), were tested and compared to constant DOT (10%) control cultures. Oscillating DOT decreased maximum cell concentrations, cell growth rates, and viability indexes. Cultures at oscillating DOT had an increased glycolytic metabolism that was evidenced by a decrease in yield of cells on glucose and an increase in lactate yield. DOT gradients, even several orders of magnitude higher than those expected under practical large-scale conditions, did not significantly affect the maximum concentration of an IgG(1) monoclonal antibody (MAb). The glycosylation profile of the MAb produced at a constant DOT of 10% was similar to that reported in the literature. However, MAb produced under oscillating culture conditions had a higher amount of triantennary and sialylated glycans, which can interfere with effector functions of the antibody. It was shown that transient excursions of hybridomas to limiting DOT, as occurs in deficiently mixed large-scale bioreactors, is important to culture performance as the oscillation period, and thus the time cells spent at low DOT, affected cell growth, metabolism, and the glycosylation pattern of MAb. Such results underline the importance of monitoring protein characteristics for the development of large-scale processes.
Conjugation to Nickel-Chelating Nanolipoprotein Particles Increases the Potency and Efficacy of Subunit Vaccines to Prevent West Nile Encephalitis (2010)

Subunit antigens are attractive candidates for vaccine development, as they are safe, cost-effective, and rapidly produced. Nevertheless, subunit antigens often need to be adjuvanted and/or formulated to produce products with acceptable potency and efficacy. Here, we describe a simple method for improving the potency and efficacy of a recombinant subunit antigen by its immobilization on nickel-chelating nanolipoprotein particles (NiNLPs). NiNLPs are membrane mimetic nanoparticles that provide a delivery and presentation platform amenable to binding any recombinant subunit immunogens featuring a polyhistidine tag. A His-tagged, soluble truncated form of the West Nile virus (WNV) envelope protein (trE-His) was immobilized on NiNLPs. Single inoculations of the NiNLP-trE-His produced superior anti-WNV immune responses and provided significantly improved protection against a live WNV challenge compared to mice inoculated with trE-His alone. These results have broad implications in vaccine development and optimization, as NiNLP technology is well-suited to many types of vaccines, providing a universal platform for enhancing the potency and efficacy of recombinant subunit immunogens.
TSU-68 (SU6668) inhibits local tumor growth and liver metastasis of human colon cancer xenografts via anti-angiogenesis (2005)

A number of receptor tyrosine kinases (RTKs) are involved in angiogenesis. TSU-68 (SU-6668) was developed as an inhibitor of RTKs involved in VEGF, bFGF and PDGF signaling, which then inhibits endothelial cell proliferation. We investigated the antitumor effects of TSU-68 against human colon cancer xenografts in male SCID mice and its anti-angiogenic activity using a dorsal air-sac (DAS) assay. TSU-68 was administered orally at a dose of 200 mg/kg twice daily. Mice bearing human colon carcinoma, HT-29, or WiDr xenografts were treated for 16 days. To determine the effect on hepatic metastasis, cell suspensions of HT-29 or WAV-I were injected into the spleen of mice on day 0, and mice treated for 28 days starting from day 1. For the DAS assay, HT-29, WiDr or WAV-I cells suspended in PBS at 2 x 10(7) cells/Millipore chamber were implanted subcutaneously into SCID mice, which were then treated from day 0 to 5, On day 6, the anti-angiogenic effects were assessed. Results indicated that TSU-68 significantly inhibited the growth of subcutaneous tumors. In the hepatic metastasis model, liver weights of the TSU-68-treated group were significantly reduced, compared to those of control mice. In the DAS assay, the angiogenic indices of the treated groups were significantly decreased for HT-29, WiDr and WAV-I tumors, with T/C ratios of 13.4, 50 and 35.3%, respectively. As TSU-68 significantly inhibited tumor growth and liver metastasis formation of human colon cancer xenografts, probably through anti-angiogenic activity, this agent may be useful for the treatment of colon cancer.
Gene targets of antisense therapies in breast cancer (2002)

Advances in molecular and cell biology have led to further understanding of the mechanisms of malignant growth and metastasis in human breast cancer cells. Initiation and progression of breast cancer results from mutations and the abnormal expression of many genes that control cellular proliferation, differentiation, invasion, metastasis and sensitivity to therapy (chemotherapy and radiation therapy). Inhibition of host immunity also plays a role in breast cancer progression. Many genes have been selected as targets for antisense therapy, including HER-2/neu, PKA, TGF-alpha, EGFR, TGF-beta, IGFIR, P12, MDM2, BRCA, Bcl-2, ER, VEGF, MDR, ferritin, transferrin receptor, IRE, C-fos, HSP27, C-myc, C-raf and metallothionein genes. The strategy behind antisense therapy is the development of specific therapeutic agents that aim to correct the mutations and abnormal expression of cellular genes in breast tumour cells by decreasing gene expression, inducing degradation of target mRNA and causing premature termination of transcription. Many in vitro and in vivo studies have investigated the therapeutic efficacy of oligonucleotides and antisense RNAs. These studies have demonstrated specific inhibition of tumour cell growth by antisense therapy and have shown synergistic inhibitory effects between antisense oligonucleotides or antisense RNA and conventional chemotherapeutic drugs used in the treatment of breast cancer. Antisense oligonucleotides have been modified to improve their ability to penetrate cells, bind to gene sequences and downregulate target gene function. Many delivery systems for antisense RNA and antisense oligonucleotides have been developed, including virus vectors (retrovirus, adenovirus and adeno-associate virus) and liposomes, to carry the antisense RNA or oligonucleotides through the cell membrane into the cytoplasm and nucleus of the tumour cells. However, in order to determine their feasibility antisense therapies need to be further investigated to determine their antitumour activity, pharmacokinetics and toxicity in breast cancer patients.
Ultra-sensitive in-situ detection of near-infrared persistent luminescent tracer nanoagents in crude oil-water mixtures (2016)

Current fluorescent nanoparticles-based tracer sensing techniques for oilfield applications suffer from insufficient sensitivity, with the tracer detection limit typically at the several hundred ppm level in untreated oil/water mixtures, which is mainly caused by the interference of the background fluorescence from the organic residues in crude oil under constant external excitation. Here we report the use of a persistent luminescence phenomenon, which enables an external excitation-free and thus background fluorescence-free measurement condition, for ultrahigh-sensitivity crude oil sensing. By using LiGa5O8:Cr(3+) near-infrared persistent luminescent nanoparticles as a tracer nanoagent, we achieved a tracer detection limit at the single-digit ppb level (down to 1 ppb concentration of nanoparticles) in high oil fraction (up to 65 wt.%) oil/water mixtures via a convenient, CCD camera-based imaging technique without any pretreatment or phase separation of the fluid samples. This detection limit is about four to five orders of magnitude lower than that obtained using conventional spectral methods. This study introduces a new type of tracer nanoagents and a new detection method for water tracer sensing in oil reservoir characterization and management.
Optical absorption of 3d transition metal and rare earth elements in zirconium fluoride glasses (1983)

Mesure des spectres d'absorption des metaux de transition 3d et des elements de terre rare dans des verres de fluorure de zirconium et evaluation de leur coefficient d'absorption dans l'infrarouge proche a moyen. Afin d'obtenir une fibre de verre de fluorure ayant une perte par transmission inferieure a 0,1 dB/km a 2,5 μm, la teneur en Fe, Co ou Nd doit etre inferieure a 1 pbb et la teneur en Ni, Pr, Sm ou Eu inferieure a 10 ppb
Assessment of the Bioactivity of Antibodies against β-Amyloid Peptide in vitro and in vivo (2004)

The accumulation of the beta-amyloid peptide (Abeta) is a central event in the pathogenesis of Alzheimer's disease (AD). Abeta removal from the brain by immune therapy shows promising potential for the treatment of patients with AD, although the mechanisms of the antibody action are incompletely understood. In this study we compared the biological activities of antibodies raised against various Abeta fragments for Abeta reduction in vitro and in vivo. Antibodies against Abeta enhanced the uptake of Abeta42 aggregates up to 6-fold by primary microglial cells in vitro. The kinetics of Abeta42 uptake varied considerably among antibodies. Based on the activity to mediate Abeta42 uptake by microglial cells, we identified a bioactive antibody that significantly reduced Abeta42 levels in the brains of transgenic mice with neuronal expression of an AD-related mutated amyloid precursor protein. This effect depended on the epitopes recognized by the antibody. Our data suggest that the ability to facilitate Abeta42 uptake by primary microglia cells in vitro can be used to predict the biological activity of the antibody by passive immunization in vivo. This protocol may prove useful for the rapid validation of the activity of antibodies designed to be used in immune therapy of AD.
Circulating microRNA Biomarkers as Liquid Biopsy for Cancer Patients: Pros and Cons of Current Assays (2015)

An increasing number of studies have focused on circulating microRNAs (cmiRNA) in cancer patients' blood for their potential as minimally-invasive biomarkers. Studies have reported the utility of assessing specific miRNAs in blood as diagnostic/prognostic biomarkers; however, the methodologies are not validated or standardized across laboratories. Unfortunately, there is often minimum limited overlap in techniques between results reported even in similar type studies on the same cancer. This hampers interpretation and reliability of cmiRNA as potential cancer biomarkers. Blood collection and processing, cmiRNA extractions, quality and quantity control of assays, defined patient population assessment, reproducibility, and reference standards all affect the cmiRNA assay results. To date, there is no reported definitive method to assess cmiRNAs. Therefore, appropriate and reliable methodologies are highly necessary in order for cmiRNAs to be used in regulated clinical diagnostic laboratories. In this review, we summarize the developments made over the past decade towards cmiRNA detection and discuss the pros and cons of the assays.
New Natural Epothilones from Sorangium cellulosum, Strains So ce90/B2 and So ce90/D13:  Isolation, Structure Elucidation, and SAR Studies (2001)

In addition to epothilones A (1) and B (2), 37 natural epothilone variants and epothilone-related compounds were isolated from the culture broth of a 700 L fermentation of Sorangium cellulosum, strain So ce90/B2. Of these, only the 12,13-desoxyepothilones, epothilone C (14) and D (15), were produced in significant amounts (3-6 mg/L); the 21-hydroxy derivatives and epothilones E (3) and F (4), in low and variable amounts due to further degradation by the producing organism. Most of the other epothilone variants were produced only in 1-100 microg/L amounts. The new compounds are very similar in structure to the parent compounds 1, 2 and 14, 15 and are presumably the result of the imperfect selectivity of the biosynthetic enzymes for acetate and propionate. Further, epothilones containing an oxazole moiety (10-13) in the side chain instead of a thiazole as well as ring-expanded 18-membered macrolides, epothilones I (30-35), and a ring contracted 14-membered macrolide, epothilone K (36), were found as very minor metabolites. The mutant strain, So ce90/D13, instead of macrolactones, produced short-chain carboxylic acids 40, 41, and 42 bearing the characteristic thiazole side chain. The structures of the new epothilones were elucidated on the basis of comprehensive NMR and MS data. The new epothilone variants were tested in a cytotoxicity assay with mouse fibroblasts (cell line L929), and structure-activity relationships were established. Several new natural epothilones showed activity comparable to 1 and 2, but in no case exceeded that of 2.
Exploiting cross-priming to generate protective CD8 T-cell immunity rapidly (2010)

The number of memory CD8 T cells generated by infection or vaccination correlates strongly with the degree of protection observed in infection and tumor models. Therefore, rapid induction of protective numbers of effector and memory CD8 T cells may be crucial in the case of malignancy, pandemic infection, or bioterrorism. Many studies have shown that amplifying T-cell numbers by prime-boost vaccination is most effective with a substantial time interval between immunizations. In contrast, immunization with peptide-coated mature dendritic cells (DCs) results in a CD8 T-cell response exhibiting accelerated acquisition of memory characteristics, including the ability to respond to booster immunization within days of initial priming. However, personalized DC immunization is too costly, labor intensive, and time-consuming for large-scale vaccination. Here, we demonstrate that in vivo cross-priming with cell-associated antigens or antigen-coated, biodegradable microspheres in the absence of adjuvant quickly generates CD8 T cells that display the phenotype and function of long-term memory populations. Importantly, cross-primed CD8 T cells can respond to booster immunization within days of the initial immunization to generate rapidly large numbers of effector and memory T cells that can protect against bacterial, viral, and parasitic infections, including lethal influenza and malaria-causing Plasmodium infection. Thus, accelerated CD8 T-cell memory after in vivo cross-priming in the absence of adjuvant is generalizable and can be exploited to generate protective immunity rapidly.