gebhart/patrepeval huggingface dataset:
Surfactant–Polymer Nanoparticles Overcome P-Glycoprotein-Mediated Drug Efflux (2007)

Nanoparticles enhance the therapeutic efficacy of an encapsulated drug by increasing and sustaining the delivery of the drug inside the cell. We have previously demonstrated that Aerosol OT (AOT)-alginate nanoparticles, a novel formulation developed recently in our laboratory, significantly enhance the therapeutic efficacy of encapsulated drugs like doxorubicin in drug-sensitive tumor cells. The purpose of this study is to evaluate the drug delivery potential of AOT-alginate nanoparticles in drug-resistant cells overexpressing the drug efflux transporter, P-glycoprotein (P-gp). AOT-alginate nanoparticles were formulated using an emulsion-cross-linking process. Rhodamine 123 and doxorubicin were used as model P-gp substrates. Cytotoxicity of nanoparticle-encapsulated doxorubicin and kinetics of nanoparticle-mediated cellular drug delivery were evaluated in both drug-sensitive and -resistant cell lines. AOT-alginate nanoparticles enhanced the cytotoxicity of doxorubicin significantly in drug-resistant cells. The enhancement in cytotoxicity with nanoparticles was sustained over a period of 10 days. Uptake studies with rhodamine-loaded nanoparticles indicated that nanoparticles significantly increased the level of drug accumulation in resistant cells at nanoparticle doses higher than 200 microg/mL. Blank nanoparticles also improved rhodamine accumulation in drug-resistant cells in a dose-dependent manner. Nanoparticle-mediated enhancement in rhodamine accumulation was not because of membrane permeabilization. Fluorescence microscopy studies demonstrated that nanoparticle-encapsulated doxorubicin was predominantly localized in the perinuclear vesicles and to a lesser extent in the nucleus, whereas free doxorubicin accumulated mainly in peripheral endocytic vesicles. Inhibition of P-gp-mediated rhodamine efflux with AOT-alginate nanoparticles was confirmed in primary brain microvessel endothelial cells. In conclusion, an AOT-alginate nanoparticle system enhanced the cellular delivery and therapeutic efficacy of P-gp substrates in P-gp-overexpressing cells.
Direct toxic effects of immunopotentiators on monocytic, myelomonocytic, and histiocytic or macrophage tumor cells in culture. (1977)

Four murine monocyte, myelomonocyte, and histiocyte or macrophage tumor cell lines adapted to culture were growth inhibited by one or more of the following macrophage-activating substances: Mycobacterium bovis, Bacillus Calmette-Guérin strain, zymosan, lipopolysaccharide, and dextran sulfate, as well as tuberculin purified protein derivative, but not latex beads. Lipopolysaccharide was effective with one line at 4 ng/ml. All four lines actively phagocytosed zymosan and latex beads. In many cases the growth inhibition was apparently immediate but only cytostatic, and cell proliferation resumed upon removal of the drug. Bacillus Calmette-Guérin, live or boiled, was toxic to some of the tumor lines. Synthesis of lysozyme by all the cell lines in the monocyte series and production of granulocyte colony-stimulating factor by the myelomonocytic leukemia were not inhibited during several days of zero growth conditions in the presence of drugs. Since these agents had no direct effect on other hematopoietic tumor types (myeloma, T-lymphoma, mastocytoma) at the same or up to 10(4) higher concentrations, it is proposed that the sensitive tumors retain specific receptors for immunostimulants, either at the cell surface or within the cell in the case of phagocytosable particles. The binding of these agents to physiological receptors leads to stimulation and mitogenesis in normal macrophages and lymphocytes but leads to growth inhibition without affecting differenetiated functions in the corresponding tumor lines.
Experimental Pretargeting Studies of Cancer with a Humanized anti-CEA × Murine anti-[In-DTPA] Bispecific Antibody Construct and a 99mTc-/188Re-Labeled Peptide (2000)

The aim of this study was to localize (99m)Tc and (188)Re radionuclides to tumors, using a bispecific antibody (bsMAb) in a two-step approach where the radionuclides are attached to novel peptides incorporating moieties recognized by one arm of the bsMAb. A chemically cross-linked human/murine bsMAb, hMN-14 x 734 (Fab' x Fab'), anti-carcinoembryonic antigen [CEA] x anti-indium-DTPA was prepared as a prelude to constructing a fully humanized bsMAb for future clinical application. N,N'-o-Phenylenedimaleimide was used to cross-link the Fab' fragments of the two antibodies at their hinge regions. This construct was shown to be >92% pure and fully reactive with CEA and a divalent (indium)DTPA-peptide. For pretargeting purposes, a peptide, IMP-192 [Ac-Lys(In-DTPA)-Tyr-Lys(In-DTPA)-Lys(TscG-Cys-)-NH(2) ¿TscG = 3-thiosemicarbazonylglyoxyl¿], with two indium-DTPAs and a chelate for selectively binding (99m)Tc or (188)Re, was synthesized. IMP-192 was formulated in a "single dose" kit and later radiolabeled with (99m)Tc (94-99%) at up to 1836 Ci/mmol and with (188)Re (97%) at 459-945 Ci/mmol of peptide. [(99m)Tc]IMP-192 was shown to be stable by extensive in vitro and in vivo testing and had no specific uptake in the tumor with minimal renal uptake. The biodistribution of the hMN-14 x murine 734 bsMAb was compared alone and in a pretargeting setting to a fully murine anti-CEA (F6) x 734 bsMAb that was reported previously [Gautherot, E., Bouhou, J., LeDoussal, J.-M., Manetti, C., Martin, M., Rouvier, E., and Barbet, J. (1997) Therapy for colon carcinoma xenografts with bispecific antibody-targeted, iodine-131-labeled bivalent hapten. Cancer 80 (Suppl.), 2618-2623]. Both bsMAbs maintained their integrity and dual binding specificity in vivo, but the hMN-14 x m734 was cleared more rapidly from the blood. This coincided with an increased uptake of the hMN-14 x m734 bsMAb in the liver and spleen, suggesting an active reticuloendothelial cell recognition mechanism of this mixed species construct in naive mice. Animals bearing GW-39 human colonic cancer xenografts were injected with bsMAb (15 microg) and after allowing 24 or 72 h for the bsMAb constructs to clear from the blood (hMN-14 and murine F6 x 734, respectively), [(188)Re]IMP-192 (7 microCi) or [(99m)Tc]IMP-192 (10 microCi) was injected at a bsMAb:peptide ratio of 10:1. Tumor uptake of [(99m)Tc] or [(188)Re]IMP-192 was 12.6 +/- 5.2 and 16.9 +/- 5.5% ID/g at 3 h postinjection, respectively. Tumor/nontumor ratios were between 5.6 and 23 to 1 for every major organ, indicating that early imaging with (99m)Tc will be possible. Radiation absorbed doses showed a 4.8-, 7.2-, and a 12.6 to 1.0 tumor to blood, kidney, and liver ratios when (188)Re was used. Although this new bsMAb pretargeting approach requires further optimization, it already shows very promising targeting results for both radioimmunodetection and radioimmunotherapy of colorectal cancer.
Tunable randomization for load management in shared-disk clusters (2005)

We develop and evaluate a system for load management in shared-disk file systems built on clusters of heterogeneous computers. It balances workload by moving file sets among cluster server nodes. It responds to changing server resources that arise from failure and recovery, and dynamically adding or removing servers. It also realizes performance consistency---nearly uniform performance across all servers. The system is adaptive and self-tuning. It operates without any a priori knowledge of workload properties, or the capabilities of the servers. Rather, it continuously tunes load placement using a technique called adaptive, nonuniform (ANU) randomization. ANU randomization realizes the scalability and metadata reduction benefits of hash-based, randomized placement techniques, while avoiding hashing's drawbacks: load skew, inability to cope with heterogeneity, and lack of tunability. ANU randomization outperforms virtual-processor approaches to load balancing, while reducing the amount of shared state among servers and the amount of load movement.
Field Case Study on Formation Fines Control With Nanoparticles in Offshore Wells (2010)

Abstract Various technologies have been developed in the industry to find efficient and cost-effective ways to control fines migration in producing wells. Migrating fines are often the source of formation near-wellbore due to their ability to choke a well's productivity by collecting in pore throats near the wellbore where flow velocity is high due to radial flow regime into the wellbore. It is important to minimize or prevent formation damage in the radial flow region around the wellbore to allow the well to operate at desired rate and bottomhole pressure. The typical recourse for formation damage resulting from migrating fines is expensive remedial stimulation treatments involving mud acid or hydraulic fracturing, which increases the well's operating cost. This paper provides a field case study of using nanoparticles to treat proppant used on an offshore frac pack. The nanoparticles have significantly high surface forces, including van der Waals forces and electrostatic forces, to attach themselves to the surface of commonly used proppant. The nanoparticles that adhere to the proppant will adsorb migrating formation fines onto the proppant surface as the fines flow into the fracture. This will maintain well productivity much longer than untreated proppant in the fracture by preventing the fines from accumulating in the near-wellbore area. After the nanoparticle-coated proppant is saturated with formation fines, it can easily be cleaned up with conventional fluids and retreated with nanoparticles for continued capturing of formation fines. The case history studies an offshore well that historically suffered systematic production loss due to migrating fines. The well was sidetracked and the new completion used nanoparticle treated proppant in the frac pack completion. After the treatment, the well's productivity was recovered and has maintained the recovered productivity for ten months without a formation fines issue.
Effects of single nightly injections of growth hormone—releasing hormone (GHRH 1–29) in healthy elderly men (1997)

Age-related reductions in growth hormone (GH) and insulin-like growth factor-I (IGF-I) may contribute to decreased muscle mass and strength in older persons. The relationship of this phenomenon to skeletal muscle bioenergetics has not been reported. We sought to determine whether administration of GH-releasing hormone (GHRH) would sustain increases in GH and IGF-I and improve skeletal muscle function and selected measures of body composition and metabolism. We measured GH secretion, muscle strength, muscle histology, and muscle energy metabolism by phosphorus nuclear magnetic resonance spectroscopy (31P-NMRS), body composition, and endocrine-metabolic functions before and after 6 weeks of treatment. Eleven healthy, ambulatory, non-obese men aged 64 to 76 years with low baseline IGF-I levels were treated at home as outpatients by nightly subcutaneous self-injections of 2 mg GHRH for 6 weeks. We measured GH levels in blood samples obtained every 20 minutes from 8:00 PM to 8:00 AM; AM serum levels of IGF-I, IGF binding protein-3 (IGFBP-3), and GH binding protein (GHBP); muscle strength; muscle histology; the normalized phosphocreatine abundance, PCr/[PCr + Pi], and intracellular pH in forearm muscle by NMRS during both sustained and ramped exercise; body composition by dual-energy x-ray absorptiometry (DEXA); lipid levels; and glucose, insulin, and GH levels during an oral glucose tolerance test (OGTT). GHRH treatment increased mean nocturnal GH release (P < .02), the area under the GH peak ([AUPGH] P < .006), and GH peak amplitude (P < .05), with no change in GH pulse frequency or in levels of IGF-I, IGFBP-3, or GHBP Two of six measures of muscle strength, upright row (P < .02) and shoulder press (P < .04), and a test of muscle endurance, abdominal crunch (P < .03), improved. GHRH treatment did not alter exercise-mediated changes in PCr/[PCr + Pi] or intracellular pH, but decreased or abolished significant relationships between changes in PCr/[PCr + Pi] or pH and indices of muscle strength. GHRH treatment did not change weight, body mass index, waist to hip ratio, DEXA measures of muscle and fat, muscle histology, glucose, insulin, or GH responses to OGTT, or lipids. No significant adverse effects were observed. These data suggest that single nightly doses of GHRH are less effective than multiple daily doses of GHRH in eliciting GH- and/or IGF-I-mediated effects. GHRH treatment may increase muscle strength, and it alters baseline relationships between muscle strength and muscle bioenergetics in a manner consistent with a reduced need for anaerobic metabolism during exercise. Thus, an optimized regimen of GHRH administration might attenuate some of the effects of aging on skeletal muscle function in older persons.
Role of Cytotoxic T Lymphocytes in Epstein-Barr Virus-Associated Diseases (2000)

Adaptation of persistent infection within the cells of the immune system is a unique characteristic of gamma herpes viruses. A classic example of this is Epstein-Barr virus (EBV), which may have co-evolved with Homo sapiens over millions of years, thus achieving a balance between viral persistence and immune control. In this review, we present an overview of virus and the host immune system interactions that regulate the life-long host-virus relationship in healthy virus carriers and EBV-associated diseases. Extensive analysis of cytotoxic T lymphocyte-mediated immune responses in healthy virus carriers has revealed unique mechanisms used by EBV to maintain a benign persistent state in vivo. On the other hand, this relationship in EBV-associated diseases favors the escape of the virus from the hostile effects of the immune response. This escape is achieved by either down-regulating the expression of highly immunogenic antigens of the virus or by direct modulation of the host cytotoxic T lymphocyte response by virus-encoded proteins.
FusariumandCandida albicansBiofilms on Soft Contact Lenses: Model Development, Influence of Lens Type, and Susceptibility to Lens Care Solutions (2007)

Fungal keratitis is commonly caused by Fusarium species and less commonly by Candida species. Recent outbreaks of Fusarium keratitis were associated with contact lens wear and with ReNu with MoistureLoc contact lens care solution, and biofilm formation on contact lens/lens cases was proposed to play a role in this outbreak. However, no in vitro model for contact lens-associated fungal biofilm has been developed. In this study, we developed and characterized in vitro models of biofilm formation on various soft contact lenses using three species of Fusarium and Candida albicans. The contact lenses tested were etafilcon A, galyfilcon A, lotrafilcon A, balafilcon A, alphafilcon A, and polymacon. Our results showed that clinical isolates of Fusarium and C. albicans formed biofilms on all types of lenses tested and that the biofilm architecture varied with the lens type. Moreover, differences in hyphal content and architecture were found between the biofilms formed by these fungi. We also found that two recently isolated keratitis-associated fusaria formed robust biofilms, while the reference ATCC 36031 strain (recommended by the International Organization for Standardization guidelines for testing of disinfectants) failed to form biofilm. Furthermore, using the developed in vitro biofilm model, we showed that phylogenetically diverse planktonic fusaria and Candida were susceptible to MoistureLoc and MultiPlus. However, Fusarium biofilms exhibited reduced susceptibility against these solutions in a species- and time-dependent manner. This in vitro model should provide a better understanding of the biology and pathogenesis of lens-related fungal keratitis.
Stability of Nucleosomes Containing Homogenously Ubiquitylated H2A and H2B Prepared Using Semisynthesis (2012)

Post-translational modifications (PTMs) of histones are an essential feature in the dynamic regulation of chromatin. One of these modifications, ubiquitylation, has been speculated to directly influence the stability of the nucleosome, which represents the basic building block of chromatin. Here we report a strategy for the semisynthesis of site-specifically ubiquitylated histone H2A (uH2A). This branched protein was generated through a three-piece expressed protein ligation approach including a traceless ligation at valine. uH2A could be efficiently incorporated into nucleosomes, thereby opening the way to detailed biochemical and biophysical studies on the function of this PTM. Accordingly, we used uH2A, as well as a previously generated ubiquitylated H2B, in chaperone-coupled nucleosome stability assays to demonstrate that the direct effect of ubiquitylated histones on nucleosomal stability is in fact modest.
Characterization and Chromosomal Localization of a cDNA Encoding Brain Amyloid of Alzheimer's Disease (1987)

Four clones were isolated from an adult human brain complementary DNA library with an oligonucleotide probe corresponding to the first 20 amino acids of the beta peptide of brain amyloid from Alzheimer's disease. The open reading frame of the sequenced clone coded for 97 amino acids, including the known amino acid sequence of this polypeptide. The 3.5-kilobase messenger RNA was detected in mammalian brains and human thymus. The gene is highly conserved in evolution and has been mapped to human chromosome 21.
NF-κB-Mediated Inhibition of Apoptosis Is Required for Encephalomyocarditis Virus Virulence: a Mechanism of Resistance in p50 Knockout Mice (1998)

Apoptosis is a central host defense mechanism to eliminate virus-infected cells. Activation of NF-kappaB suppresses apoptosis following some types of stimulation in vitro. To test the physiological importance of this pathway in vivo, we studied murine encephalomyocarditis virus (EMCV) infection in mice and cell lines defective in NF-kappaB1 (p50) signaling. As previously reported, we find that all p50 knockout (p50 -/-) mice survive an EMCV infection that readily kills normal mice. By introducing the p50 mutation into interferon (IFN) type I receptor knockout (IFNRI -/-) mice, we find that this resistance is not mediated by IFN-beta as previously thought. While no IFNRI -/- mice survive, the double-knockout mice survive 60% of the time. The survival is tightly linked to the animals' ability to clear the virus from the heart in vivo. Using murine embryonic fibroblasts (MEF) derived from wild-type, p50 -/-, and p65 -/- embryos, we found that NF-kappaB is not required for the replication cycle of EMCV. However, during these experiments we observed that p50 -/- and p65 -/- MEF infected with EMCV undergo enhanced, premature cytotoxicity. Upon examination of this cell death, we found that EMCV infection induced both plasma membrane and nuclear changes typical of apoptosis in all cell lines. These apoptotic processes occurred in an accelerated and pronounced way in the NF-kappaB-defective cells, as soon as 6 h after infection, when virus is beginning to be released. Previously, only the RelA (p65) subunit of NF-kappaB has been shown to play a role in suppressing apoptosis. In our studies, we find that p50 is equally important in suppressing apoptosis during EMCV infection. Additionally, we show that suppression of apoptosis by NF-kappaB1 is required for EMCV virulence in vivo. The attenuation in p50 -/- mice can be explained by rapid apoptosis of infected cells which allows host phagocytes to clear infected cells before the viral burst leading to a reduction of the viral burden and survival of the mice.
Ordered Reliability Bits Guessing Random Additive Noise Decoding (2021)

Modern applications are driving demand for ultra-reliable low-latency communications, rekindling interest in the performance of short, high-rate error correcting codes. To that end, here we introduce a soft-detection variant of Guessing Random Additive Noise Decoding (GRAND) called Ordered Reliability Bits GRAND that can decode any moderate redundancy block-code. For a code of n bits, it avails of no more than ⎾log <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> (n)⏋ bits of code-book-independent quantized soft detection information per received bit to determine an accurate decoding while retaining the original algorithm’s suitability for a highly parallelized implementation in hardware. ORBGRAND is shown to provide similar block error performance for codes of distinct classes (BCH, CA-Polar and RLC) with low complexity, while providing better block error rate performance than CA-SCL, a state of the art soft detection CA-Polar decoder.
Capillary Zone Electrophoresis−Electrospray Mass Spectrometry at Submicroliter Flow Rates:  Practical Considerations and Analytical Performance (1997)

A novel method for the production of coated capillaries for capillary zone electrophoresis−electrospray mass spectrometry (CZE−ESMS), operating at 100−200 nL/min flow rates is described. Electrophoretic conditions conducive to the simultaneous operation of ESMS were investigated for microsprayers of different inner diameters. The ruggedness and reliability of the CZE columns with microsprayers of 20 μm i.d. were investigated over 6 h of uninterrupted operation. Detection limits in the order of 0.1−5 fmol were obtained for peptide standards of molecular masses ranging from 500 to 2500 Da, and sensitivity was ∼10 times higher than that achieved using the more conventional sheath flow CZE−ESMS interface. Such enhancement of signal detectability provided distinct advantages for on-line line tandem mass spectrometric analyses whereby structurally informative MS−MS spectra were obtained using femtomole loadings of peptides and glycopeptides from ovalbumin digests.
Brock Biology of Microorganisms (1996)

Samenvatting:The book for introductory microbiology, Brock's Biology of Microorganismscontinues its long tradition of impeccable scholarship, outstanding art,and accuracy. It balances the most current coverage with the majorclassical concepts essential for understanding the science. A six-partpresentation covers principles of microbiology; evolutionary microbiologyand microbial diversity; metabolic diversity and microbial ecology;immunology, pathogenicity, and host responses; microbial diseases; andmicroorganisms as tools for industry and research. For researchers, groupleaders, senior scientists in pharmaceuticals, chemicals and biochemicalbiotechnology companies, and public health laboratories.
0.15 – 3.72 THz absorption of aqueous salts and saline solutions (2007)

It has recently been suggested that near-field terahertz ionic contrast microscopy can be employed to image subtle changes in ionic concentrations arising from neuronal activity. To do so, however, requires that solvated ions exhibit significant absorbance at terahertz frequencies. The authors have investigated this issue and find that, at room temperature, the molar extinctions of both sodium chloride and guanidine hydrochloride are approximately two orders of magnitude below some previous measurements and are, therefore, too low to support the proposed imaging application.