gebhart/patrepeval huggingface dataset:
Reconstituted low density lipoprotein: A vehicle for the delivery of hydrophobic fluorescent probes to cells (1979)

Previous studies have shown that the cholesteryl ester core of plasma low density lipoprotein (LDL) can be extracted with heptane and replaced with a variety of hydrophobic molecules. In the present report we use this reconstitution technique to incorporate two fluorescent probes, 3-pyrenemethyl-23, 24-dinor-5-cholen-22-oate-3 beta-yl oleate (PMCA oleate) and dioleyl fluorescein, into heptane-extracted LDL. Both fluorescent lipoprotein preparations were shown to be useful probes for visualizing the receptor-mediated endocytosis of LDL in cultured human fibroblasts. When normal fibroblasts were incubated at 37 degrees C with either of the fluorescent LDL preparations, fluorescent granules accumulated in the perinuclear region of the cell. In contrast, fibroblasts from patients with the homozygous form of familial hypercholesterolemia (FH) that lack functional LDL receptors did not accumulate visible fluorescent granules when incubated with the fluorescent reconstituted LDL. A fluorescence-activated cell sorter was used to quantify the fluorescence intensity of individual cells that had been incubated with LDL reconstituted with dioleyl fluorescein. With this technique a population of normal fibroblasts could be distinguished from a population of FH fibroblasts. The current studies demonstrate the feasibility of using fluorescent reconstituted LDL in conjunction with the cell sorter to isolate mutant cells lacking functional LDL receptors.
Epidermal Electronics (2011)

We report classes of electronic systems that achieve thicknesses, effective elastic moduli, bending stiffnesses, and areal mass densities matched to the epidermis. Unlike traditional wafer-based technologies, laminating such devices onto the skin leads to conformal contact and adequate adhesion based on van der Waals interactions alone, in a manner that is mechanically invisible to the user. We describe systems incorporating electrophysiological, temperature, and strain sensors, as well as transistors, light-emitting diodes, photodetectors, radio frequency inductors, capacitors, oscillators, and rectifying diodes. Solar cells and wireless coils provide options for power supply. We used this type of technology to measure electrical activity produced by the heart, brain, and skeletal muscles and show that the resulting data contain sufficient information for an unusual type of computer game controller.
AN ENZYMATIC FUNCTION ASSOCIATED WITH TRANSFORMATION OF FIBROBLASTS BY ONCOGENIC VIRUSES (1973)

Chick embryo fibroblast cultures develop fibrinolytic activity after transformation by Rous sarcoma virus (RSV). This fibrinolytic activity is not present in normal cultures, and it does not appear after infection with either nontransforming strains of avian leukosis viruses or cytocidal RNA and DNA viruses. In cultures infected with a temperature sensitive mutant of RSV the onset of fibrinolysis appears after exposure to permissive temperatures and precedes by a short interval the appearance of morphological evidence of transformation. See PDF for Structure The rate of fibrinolysis in transformed cultures depends on the nature of the serum that is present in the growth medium: some sera (e.g., monkey or chicken serum) promote high enzymatic activity, while others (calf, fetal bovine) do not. Some sera contain inhibitors of the fibrinolysin. Based on the effect of a small number of known inhibitors, at least one step of the fibrinolytic process shows specificity resembling that of trypsin. The sera of sarcoma-bearing chickens contain an inhibitor of the fibrinolysin, whereas normal chicken sera do not. For general discussion, conclusions, and summary see the accompanying paper, part II, (J. Exp. Med. 137:112).
Update on a tumor-associated NADH oxidase in gastric cancer cell growth (2016)

Gastric cancer is one of the most common human malignancies, and its prevalence has been shown to be well-correlated with cancer-related deaths worldwide. Regrettably, the poor prognosis of this disease is mainly due to its late diagnosis at advanced stages after the cancer has already metastasized. Recent research has emphasized the identification of cancer biomarkers in the hope of diagnosing cancer early and designing targeted therapies to reverse cancer progression. One member of a family of growth-related nicotinamide adenine dinucleotide (NADH or hydroquinone) oxidases is tumor-associated NADH oxidase (tNOX; ENOX2). Unlike its counterpart CNOX (ENOX1), identified in normal rat liver plasma membranes and shown to be stimulated by growth factors and hormones, tNOX activity purified from rat hepatoma cells is constitutively active. Its activity is detectable in the sera of cancer patients but not in those of healthy volunteers, suggesting its clinical relevance. Interestingly, tNOX expression was shown to be present in an array of cancer cell lines. More importantly, inhibition of tNOX was well correlated with reduced cancer cell growth and induction of apoptosis. RNA interference targeting tNOX expression in cancer cells effectively restored non-cancerous phenotypes, further supporting the vital role of tNOX in cancer cells. Here, we review the regulatory role of tNOX in gastric cancer cell growth.
Minimal residual disease negativity using deep sequencing is a major prognostic factor in multiple myeloma (2018)

The introduction of novel agents has led to major improvements in clinical outcomes for patients with multiple myeloma. To shorten evaluation times for new treatments, health agencies are currently examining minimal residual disease (MRD) as a surrogate end point in clinical trials. We assessed the prognostic value of MRD, measured during maintenance therapy by next-generation sequencing (NGS). MRD negativity was defined as the absence of tumor plasma cell within 1 000 000 bone marrow cells (<10<sup>-6</sup>). Data were analyzed from a recent clinical trial that evaluated the role of transplantation in newly diagnosed myeloma patients treated with lenalidomide, bortezomib, and dexamethasone (RVD). MRD negativity was achieved at least once during maintenance in 127 patients (25%). At the start of maintenance therapy, MRD was a strong prognostic factor for both progression-free survival (adjusted hazard ratio, 0.22; 95% confidence interval, 0.15-0.34; <i>P</i> < .001) and overall survival (adjusted hazard ratio, 0.24; 95% confidence interval, 0.11-0.54; <i>P</i> = .001). Patients who were MRD negative had a higher probability of prolonged progression-free survival than patients with detectable residual disease, regardless of treatment group (RVD vs transplant), cytogenetic risk profile, or International Staging System disease stage at diagnosis. These results were similar after completion of maintenance therapy. Our findings confirm the value of MRD status, as determined by NGS, as a prognostic biomarker in multiple myeloma, and suggest that this approach could be used to adapt treatment strategies in future clinical trials.
La innovación tecnológica como herramienta para el desarrollo de la competitividad en las pymes (2013)

Las compañías pequeñas responden de manera más cercana a las demandas del mercado, en comparación con las grandes compañías; por lo que estas compañías pequeñas disfrutan de un ventaja competitiva relacionada a una burocracia más pequeña; eficiente, algunas veces informal, sistemas de información internos, y una flexibilidad y adaptabilidad a través de la cercanía con el mercado. En contraste, las pequeñas compañías presentan una serie de limitaciones por la falta de: trabajadores técnicamente calificados, uso pobre de la información externa y experiencia; dificultad en la atracción de financiamientos y seguridad financiera, relacionado todo esto con la poca capacidad para tomar riesgos en inversiones; inusual administración desde el inicio del negocio; y un alto costo para operar dentro del margen regulatorio. En esencia, la ventaja de las pequeñas compañías se ve reflejada en su comportamiento fundamentalmente, con lo cual puede generar innovaciones.
Learning table access cardinalities with LEO (2002)

LEO is a comprehensive way to repair incorrect statistics and cardinality estimates of a query execution plan. LEO introduces a feedback loop to query optimization that enhances the available information on the database where the most queries have occurred, allowing the optimizer to actually learn from its past mistakes. We demonstrate how LEO learns outdated table access statistics on a TPC-H like database schema and show that LEO improves the estimates for table cardinalities as well as filter factors for single predicates. Thus LEO enables the query optimizer to choose a better query execution plan, resulting in more efficient query processing. We not only demonstrate learning by repetitive execution of a single query, but also illustrate how similar, but not identical queries benefit from learned knowledge. In addition, we show the effect of both learning cardinalities and adjusting related statistics.
Molecular docking towards drug discovery (1996)

Fueled by advances in molecular structure determination, tools for structure-based drug design are proliferating rapidly. Lead discovery through searching of ligand databases with molecular docking techniques represents an attractive alternative to high-throughout random screening. The size of commercial databases imposes severe computational constraints on molecular docking, compromising the level of calculational detail permitted for each putative ligand. We describe alternative philosophies for docking which effectively address this challenge. With respect to the dynamic aspects of molecular recognition, these strategies lie along a spectrum of models bounded by the Lock-and-Key and Induced-Fit theories for ligand binding. We explore the potential of a rigid model in exploiting species specificity and of a tolerant model in predicting absolute ligand binding affinity. Current molecular docking methods are limited primarily by their ability to rank docked complexes; we therefore place particular emphasis on this aspect of the problem throughout our validation of docking strategies.
Phasing of a two-channel continuous-wave master oscillator–power amplifier by use of a fiber phase-conjugate mirror (2005)

Phasing of two-channel cw master-oscillator-power-amplifier beams by using a phase-conjugate mirror has been demonstrated for the first time to the best of our knowledge. Phasing was achieved with two fiber amplifiers in conjunction with a single-frequency Nd:YAG master oscillator by using a fiber phase-conjugate mirror in a double-pass geometry. The successful demonstration of phasing of two cw amplifier beams with a fiber phase-conjugate mirror greatly enhances the prospects for phasing of multiple laser amplifiers without complex servo-loop control systems.
Analytical approaches to detection and characterization of disease-linked chromosome aberrations. (1990)

Flow karyotyping and FISH with chromosome specific or disease-locus-specific probes are powerful adjuncts to conventional cytogenetic analysis. Flow karyotyping is well suited to quantitative analysis of DNA content changes that occur during structural rearrangement. FISH with probes for repeated sequences allows ready detection of aneuploidy in interphase cells. FISH with whole chromosome composite probes to metaphase spreads facilitates detection of subtle structural changes and allows detection of structural aberrations that occur at frequencies as low as 10(-3). FISH with locus-specific probes facilitates diagnosis of specific genetic diseases, allows phenotype-genotype correlation on a cell-by-cell basis and may be developed into a sensitive method for detection of residual disease.
Strategies for protecting oligodendrocytes and enhancing remyelination in multiple sclerosis. (2013)

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) characterized by encephalitogenic leukocyte infiltration and multifocal plaques of demyelination. Patients present with debilitating clinical sequelae including motor, sensory, and cognitive deficits. For the past 30 years, immune modulating treatments have entered the marketplace and continue to improve in limiting the frequency and severity of relapses, but no cure has been found and no drug has successfully stopped chronic progressive disease. Recent work focusing on the oligodendrocyte, the myelin-producing cell, has provided needed insight into the process of demyelination, the spontaneous ability of the CNS to regenerate, and the inevitable failure of remyelination. From this a number of promising molecular targets have been identified to protect oligodendrocytes and promote remyelination. Combining immunomodulatory therapy with strategies to protect oligodendrocytes from further degeneration and enhance remyelination presents a very real means to improve clinical outcome for chronic progressive patients in the near future. Here we lay out a combination therapy approach to treating MS and survey the current literature on promising drug candidates potentially capable of mediating oligodendrocyte protection and enhancing remyelination.
Significance of Noninvasive Diagnosis of Prostate Cancer with Cytologic Examination of Prostatic Fluid (2006)

Exfoliative cytologic examination of PF is a valuable, noninvasive method for detecting prostate cancer, especially in patients with high PSA levels.
Lactate kinetics at the lactate threshold in trained and untrained men (2013)

To understand the meaning of the lactate threshold (LT) and to test the hypothesis that endurance training augments lactate kinetics [i.e., rates of appearance and disposal (Ra and Rd, respectively, mg·kg(-1)·min(-1)) and metabolic clearance rate (MCR, ml·kg(-1)·min(-1))], we studied six untrained (UT) and six trained (T) subjects during 60-min exercise bouts at power outputs (PO) eliciting the LT. Trained subjects performed two additional exercise bouts at a PO 10% lower (LT-10%), one of which involved a lactate clamp (LC) to match blood lactate concentration ([lactate]b) to that achieved during the LT trial. At LT, lactate Ra was higher in T (24.1 ± 2.7) than in UT (14.6 ± 2.4; P < 0.05) subjects, but Ra was not different between UT and T when relative exercise intensities were matched (UT-LT vs. T-LT-10%, 67% Vo2max). At LT, MCR in T (62.5 ± 5.0) subjects was 34% higher than in UT (46.5 ± 7.0; P < 0.05), and a reduction in PO resulted in a significant increase in MCR by 46% (LT-10%, 91.5 ± 14.9, P < 0.05). At matched relative exercise intensities (67% Vo2max), MCR in T subjects was 97% higher than in UT (P < 0.05). During the LC trial, MCR in T subjects was 64% higher than in UT (P < 0.05), in whom %Vo2max and [lactate]b were similar. We conclude that 1) lactate MCR reaches an apex below the LT, 2) LT corresponds to a limitation in MCR, and 3) endurance training augments capacities for lactate production, disposal and clearance.
Circulating Pro- and Counterinflammatory Cytokine Levels and Severity in Necrotizing Enterocolitis (1999)

The severity of NEC and its systemic signs and symptoms are not due to a deficiency of counterregulatory cytokines. In fact, mean concentrations of IL-1ra in NEC are higher than what has been reported in other populations. The cytokines IL-8, IL-1ra, and IL-10 are released later or more slowly after a stimulus and may be more useful in identifying, within hours of symptom onset, which infant will develop significant NEC.
Two- and three-input TALE-based AND logic computation in embryonic stem cells (2013)

Biological computing circuits can enhance our ability to control cellular functions and have potential applications in tissue engineering and medical treatments. Transcriptional activator-like effectors (TALEs) represent attractive components of synthetic gene regulatory circuits, as they can be designed de novo to target a given DNA sequence. We here demonstrate that TALEs can perform Boolean logic computation in mammalian cells. Using a split-intein protein-splicing strategy, we show that a functional TALE can be reconstituted from two inactive parts, thus generating two-input AND logic computation. We further demonstrate three-piece intein splicing in mammalian cells and use it to perform three-input AND computation. Using methods for random as well as targeted insertion of these relatively large genetic circuits, we show that TALE-based logic circuits are functional when integrated into the genome of mouse embryonic stem cells. Comparing construct variants in the same genomic context, we modulated the strength of the TALE-responsive promoter to improve the output of these circuits. Our work establishes split TALEs as a tool for building logic computation with the potential of controlling expression of endogenous genes or transgenes in response to a combination of cellular signals.
Posttranscriptional regulation of cellular gene expression by the c-myc oncogene. (1989)

The c-myc oncogene has been implicated in the development of many different cancers, yet the mechanism by which the c-myc protein alters cellular growth control has proven elusive. We used a cDNA hybridization difference assay to isolate two genes, mr1 and mr2, that were constitutively expressed (i.e., deregulated) in rodent fibroblast cell lines immortalized by transfection of a viral promoter-linked c-myc gene. Both cDNAs were serum inducible in quiescent G0 fibroblasts, suggesting that they are functionally related to cellular proliferative processes. Although there were significant differences in cytoplasmic mRNA levels between myc-immortalized and control cells, the rates of transcription and mRNA turnover of both genes were similar, suggesting that c-myc regulates mr1 and mr2 expression by some nuclear posttranscriptional mechanism. mr1 was also rapidly (within 2 h) and specifically induced by dexamethasone in BALB/c cell lines expressing a mouse mammary tumor virus long terminal repeat-driven myc gene, under conditions where other growth factor-inducible genes were unaffected. A frameshift mutation in the mouse mammary tumor virus myc gene destroyed the dexamethasone stimulation of mr1, indicating that c-myc protein is required for the effect. As in the myc-immortalized cells, the induction of mr1 by c-myc occurred without detectable changes in mr1 transcription or cytoplasmic mRNA stability, implicating regulation, either direct or indirect, through a nuclear posttranscriptional mechanism. These results provide evidence that c-myc can rapidly modulate cellular gene expression and suggest that c-myc may function in gene regulation at the level of RNA export, splicing, or nuclear RNA turnover.
Ca 2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity (2004)

Human Rad51 (hRad51) protein plays a key role in homologous recombination and DNA repair. hRad51 protein forms a helical filament on single-stranded DNA (ssDNA), which performs the basic steps of homologous recombination: a search for homologous double-stranded DNA (dsDNA) and DNA strand exchange. hRad51 protein possesses DNA-dependent ATPase activity; however, the role of this activity has not been understood. Our current results show that Ca(2+) greatly stimulates DNA strand exchange activity of hRad51 protein. We found that Ca(2+) exerts its stimulatory effect by modulating the ATPase activity of hRad51 protein. Our data demonstrate that, in the presence of Mg(2+), the hRad51-ATP-ssDNA filament is quickly converted to an inactive hRad51-ADP-ssDNA form, due to relatively rapid ATP hydrolysis and slow dissociation of ADP. Ca(2+) maintains the active hRad51-ATP-ssDNA filament by reducing the ATP hydrolysis rate. These findings demonstrate a crucial role of the ATPase activity in regulation of DNA strand exchange activity of hRad51 protein. This mechanism of Rad51 protein regulation by modulating its ATPase activity is evolutionarily recent; we found no such mechanism for yeast Rad51 (yRad51) protein.
NONDESTRUCTIVE INSPECTION OF COMPOSITE STRUCTURES: METHODS AND PRACTICE (2008)

Composite materials are widely used in a number of industrial sectors from aviation, space, to boat building, automotive, and sports goods. In recent years composite structures have seen a substantial increase of their use in the new generation of airplanes. The nondestructive testing and inspection of composite structures, both for manufacturing quality assurance and for in-service damage detection, has prompted the development and adaptation of a number of methods and techniques over the years. In this paper we review the various NDT methods for inspecting composites, especially those developed by the Center for Nondestructive Evaluation at Iowa State University in its interaction with the industrial users of composites. We will address the inspection issues of different types of composite structures including solid laminates, honeycomband foam-core sandwich components, and touch upon the inspection of perforated facesheets and bonded aluminum structures. The capability of various NDT methods including water- and air-coupled ultrasound, bond testing, manual and automated tap testing, thermography, and shearography will be described, with emphasis given to techniques that demonstrated benefits to the practice of composite inspection. Techniques developed by Iowa State University for performing composite inspections in the field, especially those with imaging capability, will be described.
Critical role for phosphoinositide 3-kinase gamma in parasite invasion and disease progression of cutaneous leishmaniasis (2012)

Obligate intracellular pathogens such as Leishmania specifically target host phagocytes for survival and replication. Phosphoinositide 3-kinase γ (PI3Kγ), a member of the class I PI3Ks that is highly expressed by leukocytes, controls cell migration by initiating actin polymerization and cytoskeletal reorganization, which are processes also critical for phagocytosis. In this study, we demonstrate that class IB PI3K, PI3Kγ, plays a critical role in pathogenesis of chronic cutaneous leishmaniasis caused by L. mexicana. Using the isoform-selective PI3Kγ inhibitor, AS-605240 and PI3Kγ gene-deficient mice, we show that selective blockade or deficiency of PI3Kγ significantly enhances resistance against L. mexicana that is associated with a significant suppression of parasite entry into phagocytes and reduction in recruitment of host phagocytes as well as regulatory T cells to the site of infection. Furthermore, we demonstrate that AS-605240 is as effective as the standard antileishmanial drug sodium stibogluconate in treatment of cutaneous leishmaniasis caused by L. mexicana. These findings reveal a unique role for PI3Kγ in Leishmania invasion and establishment of chronic infection, and demonstrate that therapeutic targeting of host pathways involved in establishment of infection may be a viable strategy for treating infections caused by obligate intracellular pathogens such as Leishmania.
Prognostic and Predictive Value inKRASin Non–Small-Cell Lung Cancer (2016)

KRAS is one of the most common oncogenic driver mutations in NSCLC, with prior attempts at direct inhibition being unsuccessful. In recent years, there has been significant advancement in the understanding of the biology of KRAS and its downstream effectors. This has translated into a multitude of important preclinical studies and clinical trials that are currently underway to find effective therapeutic drugs for KRAS mutant lung cancer. Ultimately, better therapeutics need to be engineered to arrive at RAS-driven precision medicine.
Silybin-beta-cyclodextrin in the treatment of patients with diabetes mellitus and alcoholic liver disease. Efficacy study of a new preparation of an anti-oxidant agent. (2002)

Oral administration silybin-beta-cyclodextrin in patients with T2DM and compensated chronic alcoholic liver disease causes a significant decrease in both glucose and triglyceride plasma levels. These effects may be due to the recovery of energy substrates, consistent with a reduced lipid peroxidation and an improved insulin activity.