gebhart/patrepeval huggingface dataset:
Constitutive expression of hepatic cytochrome P450 genes (1996)

Cytochromes P450 are a superfamily of heme proteins involved in oxidative metabolism of endogenous chemicals such as steroid hormones and human-made xenobiotics including drugs and environmental pollutants. Hundreds of P450s have been demonstrated by cDNA and gene cloning in animals, plants, fungi, and bacteria. Most of the mammalian xenobiotic-metabolizing P450s, found within the eight subfamilies comprising the CYP2 family, are constitutively expressed in the liver. Transcriptional activation of individual P450 genes in the liver commences at distinct stages of development. Some P450 genes are preferentially expressed in one sex. The mechanisms of liver-specific expression of the P450 genes are quite diverse. Recent studies have found that several different liver-enriched transcription factors including HNF-1 alpha, HNF-3, HNF-4, and C/EBP beta, and the more ubiquitously expressed factors Sp1, GABP alpha/beta, and NF2d9 are responsible for governing the transcription of P450 genes. In some cases, more than one factor can influence expression depending on the developmental stage of the animal, and ubiquitously expressed factors such as Sp1 have been found to cooperate with liver-enriched factors to maximally activate transcription of P450 genes. STAT protein- and phospholipase A2-mediated signal transduction have also been implicated in sex-dependent expression of certain P450 genes. These studies indicate that P450 genes, even within the same subfamily in the same mammalian species, can have unique regulatory circuits.-Gonzalez, F. J., Lee, Y.-H. Constitutive expression of hepatic cytochrome P450 genes.
Stress-induced tRNA-derived RNAs: a novel class of small RNAs in the primitive eukaryote Giardia lamblia (2008)

Giardia lamblia is an early diverging and evolutionarily successful protozoan as it can enter into a dormant cyst stage from a vegetative trophozoite. During dormant stage, its metabolic rate decreases dramatically. However, to date, the regulatory molecules participating in the initiation and maintenance of this process have not been fully investigated. In this study, we have identified a class of abundant small RNAs named sitRNAs, which are approximately 46 nucleotides in length and accumulate in G. lamblia encysting cultures. Remarkably, they are derived from the 3' portion of fully matured tRNAs by cleavage of the anticodon left arm, with the 3' terminal CCA triplex still connected. During differentiation, only a limited portion of mature tRNAs is cleaved, but this cleavage occurs almost in the entire tRNA family. sitRNAs begin to accumulate as early as 3 h after initiation of encystation and are maintained at a relatively stable level during the whole process, exhibiting an expression peak at around 24 hr. Our studies further show that sitRNAs can be induced by several other stress factors, and in the case of serum deprivation, both tRNAs and sitRNAs degrade rapidly, with the accumulation of tRNA being halved. Our results may provide new insight into a novel mechanism for stressed G. lamblia to regulate gene expression globally.
Targeting the Insulin-like Growth Factor Receptor-1R Pathway for Cancer Therapy (2010)

Signaling through the insulin-like growth factor receptor (IGF-1R) is required for neoplastic transformation by a number of oncogenes, and preclinical validation studies have suggested IGF-1R is an attractive target for anticancer therapy. A number of small molecules and antibodies targeting IGF-1R have entered clinical development, and early results have suggested that these agents have generally acceptable safety profiles as single agents. Some evidence of antitumor activity has also been reported. This review highlights key aspects of the IGF-1R signaling pathway that implicate it as an attractive therapeutic target in the management of cancer, as well as some key lessons that have emerged from early clinical development of anti-IGF-1R targeting agents. In addition, we consider the importance of selecting indications characterized by pathological alterations in the signaling pathway, rational selection of combinations based on signaling pathway interactions, and strategies for patient selection based on analysis of predictive biomarkers.
ATP-Mediated Glia Signaling (2000)

Glia calcium signaling has recently been identified as a potent modulator of synaptic transmission. We show here that the spatial expansion of calcium waves is mediated by ATP and subsequent activation of purinergic receptors. Ectopic expression of gap junction proteins, connexins (Cxs), leads to an increase in both ATP release and the radius of calcium wave propagation. Cx expression was also associated with a phenotypic transformation, and cortical neurons extended longer neurites when co-cultured with Cx-expressing than with Cx-deficient cells. Purinergic receptor activation mediated both these effects, because treatment with receptor antagonists restored the glia phenotype and slowed neurite outgrowth. These results identify a key role of ATP in both short-term calcium signaling events and in long-term differentiation regulated by glia.
Potassium currents responsible for inward and outward rectification in rat neostriatal spiny projection neurons (1995)

Many of the nonlinear membrane properties displayed by neostriatal spiny projection neurons are conferred by their voltage-gated potassium (K+) currents, including an inwardly rectifying current (IKir), fast (IAt), and slowly (IAs)-inactivating A-currents, and a slow, noninactivating current. The relative contribution of these K+ currents to the pronounced inward and outward rectification of the current-voltage (I-V) relationship of spiny neurons was investigated in a neostriatal slice preparation. Manipulation of the equilibrium potential for K+ (EK) showed that the voltage dependence of activation of inward rectification was identical to that of IKir. In addition, application of barium (100 microM), which is known to reduce IKir in a time- and voltage-dependent manner, had equivalent effects on inward rectification. Subsequent application of cesium (3 mM) or tetraethylammonium (TEA, 25 mM) blocked inward rectification in a solely voltage-dependent fashion consistent with the action of these blockers on IKir. Administration of 4-aminopyridine (4-AP, 100 microM) at concentrations that selectively depress IAs, reduced outward rectification of spiny neurons at subthreshold membrane potentials. Higher concentrations of 4-AP (2 mM), which block both IAs and IAt, revealed an early transient overshoot in voltage deflections at potentials near spike threshold, but rectification persisted at the end of the responses. The transient overshoot and the residual rectification were eliminated by TEA (25 mM), a blocker of the slow, noninactivating K+ current. Collectively, these results indicate that all three depolarization-activated K+ currents contribute to outward rectification at different times and membrane potentials defined by their voltage dependence of activation and kinetics of inactivation. The spontaneous activity of neostriatal spiny neurons recorded in intact animals is characterized by sustained and limited shifts in membrane potential from relatively hyperpolarized potentials to depolarized potentials near spike threshold. The present data suggest that the hyperpolarized state is determined principally by IKir and the limits on the depolarized state are defined by IAf, IAs, and the noninactivating current. These outward K+ currents also are hypothesized to govern the spike discharge characteristics once the depolarized state has been reached.
Carbon nanotube materials for aerospace wiring (2010)

With large amounts of time and money invested in the advancement of aerospace structures, the performance and reliability are crucial factors in the development of new components to extend the lifetime of these spacecrafts. Wires composed of long, highly aligned, and defect-free carbon nanotubes (CNTs) could have a great impact on aerospace, military, and industrial applications which require lightweight and durable electrically conductive materials. Carbon nanotubes represent an ideal material which is not only electrically conductive, but also exhibits resistance to oxidation, radiation tolerance, and mechanical robustness. Highly conductive bulk carbon nanotube wires were drawn to meter lengths using a drawing die process. A series of solvents were investigated as potential lubricants to improve the process as well as the electrical and mechanical properties of the resulting wires. Inorganic and organic chemical doping was used in conjunction with densification to increase the electrical conductivity of the wires, achieving a maximum conductivity of 1.3 x 106 S/m. Temperature dependent electrical conductivity measurements were recorded to evaluate the fundamental electrical conduction mechanism in CNT wires resulting from the doping and densification processes. These measurements indicated that the electron tunneling barrier between adjacent CNTs can be drastically reduced by ionic doping and densification. Furthermore, a novel technique of contacting CNT wires to metals via ultrasonic welding was reported with mechanical and electrical characterization of the welds achieved. Lastly, real world demonstrations of the power and data transmission capabilities of these CNT wires were constructed and tested, specifically a USB cable and coaxial wires.
Closure of skin incisions in rabbits by laser soldering II: Tensile strength (2004)

Temperature-controlled laser soldering at 65 degrees C provided sufficient ITS and higher bonding LTS values compared with sutures, resulting in better wound healing characteristics. The laser soldering system presented here should be tested on larger animal models before adopting it for clinical usage.
β-Amyloid peptides enhance α-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease (2001)

Alzheimer's disease and Parkinson's disease are associated with the cerebral accumulation of beta-amyloid and alpha-synuclein, respectively. Some patients have clinical and pathological features of both diseases, raising the possibility of overlapping pathogenetic pathways. We generated transgenic (tg) mice with neuronal expression of human beta-amyloid peptides, alpha-synuclein, or both. The functional and morphological alterations in doubly tg mice resembled the Lewy-body variant of Alzheimer's disease. These mice had severe deficits in learning and memory, developed motor deficits before alpha-synuclein singly tg mice, and showed prominent age-dependent degeneration of cholinergic neurons and presynaptic terminals. They also had more alpha-synuclein-immunoreactive neuronal inclusions than alpha-synuclein singly tg mice. Ultrastructurally, some of these inclusions were fibrillar in doubly tg mice, whereas all inclusions were amorphous in alpha-synuclein singly tg mice. beta-Amyloid peptides promoted aggregation of alpha-synuclein in a cell-free system and intraneuronal accumulation of alpha-synuclein in cell culture. beta-Amyloid peptides may contribute to the development of Lewy-body diseases by promoting the aggregation of alpha-synuclein and exacerbating alpha-synuclein-dependent neuronal pathologies. Therefore, treatments that block the production or accumulation of beta-amyloid peptides could benefit a broader spectrum of disorders than previously anticipated.
Charge carrier trapping effect by luminescent dopant molecules in single-layer organic light emitting diodes (1999)

We investigated electroluminescent (EL) characteristics of single-layer organic light emitting diodes (SOLEDs). Our SOLED devices are composed of an inert polymer as a binder, in which hole transport molecules, emissive electron transport molecules (ETMs), and highly fluorescent dopants as luminescent centers are dispersed. We examined two typical dopants: rubrene and coumarin 6. These exhibited different charge carrier recombination and emission mechanisms. The dopant concentration dependence of the current density–voltage–luminance relationships clearly showed the importance of carrier trapping by dopant molecules for obtaining high luminance. When the dopant was rubrene, we observed that charge carriers were well trapped by the dopant molecule. This means that direct recombination of holes and electrons occurred on the dopant molecules and trapping significantly enhanced the external EL quantum efficiency ΦEL. For coumarin 6, on the other hand, we observed that charge carriers primarily recombined at the emissive ETMs and that the energy transfer from the host to the guest coumarin 6 molecule dominated the EL process. A comparison of these distinct processes revealed that carrier trapping by dopant molecules was necessary to enhance ΦEL in SOLED devices. In our best SOLED device with rubrene as a dopant, we measured luminance of 2800 cd/m2 at J=100 mA/cm2, which corresponds to ΦEL=0.85%.
Decreased synthesis and vasodilation to nitric oxide in piglets with hypoxia-induced pulmonary hypertension (2000)

Nitric oxide (NO) is thought to play an important role in the regulation of neonatal pulmonary vasculature. It has been suggested that neonates with pulmonary hypertension have a defective NO pathway. Therefore, we measured in 1-day-old piglets exposed to hypoxia (fraction of inspired O(2) = 0.10) for 3 or 14 days to induce pulmonary hypertension 1) the activity of NO synthase (NOS) via conversion of L-arginine to L-citrulline and the concentration of the NO precursor L-arginine in isolated pulmonary vessels, 2) the vasodilator response to the NO donor 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1) and the cGMP analog 8-bromo-cGMP in isolated perfused lungs, and 3) the production of cGMP in response to SIN-1 in isolated perfused lungs. After 3 days of exposure to hypoxia, endothelial NOS (eNOS) activity was unaffected, whereas, after 14 days of hypoxia, eNOS activity was decreased in the cytosolic fraction of pulmonary artery (P < 0.05) but not of pulmonary vein homogenates. Inducible NOS activity was decreased in the cytosolic fraction of pulmonary artery homogenates after both 3 (P < 0.05) and 14 (P < 0.05) days of hypoxia but was unchanged in pulmonary veins. Pulmonary artery levels of L-arginine were unaffected by hypoxic exposure. After 3 days of exposure to hypoxia, the reduction in the dilator response to SIN-1 (P < 0.05) coincided with a decrease in cGMP production (P < 0.005), suggesting that soluble guanylate cyclase activity may be altered. When the exposure was prolonged to 14 days, dilation to SIN-1 remained decreased (P < 0.05) and, although cGMP production normalized, the dilator response to 8-bromo-cGMP decreased (P < 0.05), suggesting that, after prolonged exposure to hypoxia, cGMP-dependent mechanisms may also be impaired. In conclusion, neonatal hypoxia-induced pulmonary hypertension is associated with multiple disruptions in the NO pathway.
Tumor necrosis factor-α synthesis inhibitor 3,6′-dithiothalidomide attenuates markers of inflammation, Alzheimer pathology and behavioral deficits in animal models of neuroinflammation and Alzheimer’s disease (2012)

Our data suggest a strong beneficial effect of 3,6'-dithiothalidomide in the setting of neuroinflammation and AD, supporting a role for neuroinflammation and TNF-α in disease progression and their targeting as a means of clinical management.
Gene Therapy for Hemophilia: Clinical Trials and Technical Tribulations (2009)

As monogenic disorders, hemophilia A and B are compelling candidates for treatment with gene therapy. In hemophilia, a therapeutic benefit achieved by gene therapy should only require a modest increase in the endogenous factor level; response to treatment can be monitored easily; and there are relevant small and large animal models. The two main approaches aiming to restore factor VIII or factor IX production are based on genetically modified cells or direct in vivo gene delivery using viral or plasmid vectors. The progress toward gene therapy for hemophilia A and B in both preclinical and clinical models will be evaluated in this review. Various viral and nonviral vectors are discussed in the context of current hurdles arising from preclinical and clinical trials. Despite disappointing clinical results to date, there are favorable indications that the near future should deliver on the long-sought promise of a cure for hemophilia.
SKI-606, a Src/Abl Inhibitor withIn vivoActivity in Colon Tumor Xenograft Models (2005)

Src up-regulation is a common event in human cancers. In colorectal cancer, increased Src levels are an indicator of poor prognosis, and progression to metastatic disease is associated with substantial increases in Src activity. Therefore, we examined the activity of SKI-606, a potent inhibitor of Src and Abl kinases, against colon tumor lines in vitro and in s.c. tumor xenograft models. SKI-606 inhibited Src autophosphorylation with an IC(50) of approximately 0.25 micromol/L in HT29 cells. Phosphorylation of Tyr(925) of focal adhesion kinase, a Src substrate, was reduced by similar concentrations of inhibitor. Antiproliferative activity on plastic did not correlate with Src inhibition in either HT29 or Colo205 cells (IC(50)s, 1.5 and 2.5 micromol/L, respectively), although submicromolar concentrations of SKI-606 inhibited HT29 cell colony formation in soft agar. SKI-606 also caused loosely aggregated Colo205 spheroids to condense into compact spheroids. On oral administration to nude mice at the lowest efficacious dose, peak plasma concentrations of approximately 3 micromol/L, an oral bioavailability of 18%, and a t(1/2) of 8.6 hours were observed. SKI-606 was orally active in s.c. colon tumor xenograft models and caused substantial reductions in Src autophosphorylation on Tyr(418) in HT29 and Colo205 tumors. SKI-606 inhibited HT29 tumor growth on once daily administration, whereas twice daily administration was necessary to inhibit Colo205, HCT116, and DLD1 tumor growth. These results support development of SKI-606 as a therapeutic agent for treatment of colorectal cancer.
Automation Controller for Operational IT Management (2007)

Controllers in computer systems have mainly been explored for automating regulative tasks such as admission control or resource supply control. The majority of IT management tasks, however, relies on discrete management states and coordinated transitions between those states. The paper shows how the concept of a feedback system can also be applied to automate operational management tasks. The paper introduces the concept and a realization of an IT management automation controller, which operates on discrete management states expressed as a pair of models for desired and observed state. Models are represented as a special form of place-transition nets (PTN or Petri nets). Controller logic directly executes PTN in order to achieve and maintain alignment between desired and observed state in a managed domain. In contrast to workflow systems, PTN combine the description of state and actions in one model (graph). Three operational database management tasks have been implemented as a proof of concept in a blade server automation infrastructure using the management automation controller.
The Human Genus (1999)

A general problem in biology is how to incorporate information about evolutionary history and adaptation into taxonomy. The problem is exemplified in attempts to define our own genus, Homo. Here conventional criteria for allocating fossil species to Homo are reviewed and are found to be either inappropriate or inoperable. We present a revised definition, based on verifiable criteria, for Homo and conclude that two species, Homo habilis and Homo rudolfensis, do not belong in the genus. The earliest taxon to satisfy the criteria is Homo ergaster, or early African Homo erectus, which currently appears in the fossil record at about 1.9 million years ago.
Genes for immunodominant protein antigens are highly homologous in Mycobacterium tuberculosis, Mycobacterium africanum, and the vaccine strain Mycobacterium bovis BCG (1987)

The relatedness of immunodominant protein antigens in Mycobacterium tuberculosis, M. africanum, and M. bovis BCG was investigated by comparing the genes that encode major protein antigens in M. tuberculosis with their counterparts in the other two mycobacteria. Genes encoding homologs of M. tuberculosis major protein antigens were isolated from M. africanum and M. bovis BCG by constructing lambda gt11 recombinant DNA expression libraries and screening them with murine monoclonal antibodies and DNA probes. The antibodies were directed against four major protein antigens of M. tuberculosis with molecular masses of 71, 65, 19, and 14 kilodaltons. The isolated M. africanum and M. bovis BCG DNA clones were mapped with restriction endonucleases, and the maps of the mycobacterial genes were confirmed by Southern analysis of mycobacterial genomic DNA. The restriction maps of DNA containing the four genes in M. tuberculosis, M. africanum, and M. bovis BCG are identical, indicating that the immunodominant proteins that they encode are highly homologous in the three mycobacteria. Thus, the immunity against tuberculosis engendered by M. bovis BCG vaccination could be provided, at least in part, by the immune response to these homologous antigens.
Combinatorial materials synthesis and high-throughput screening: An integrated materials chip approach to mapping phase diagrams and discovery and optimization of functional materials (1999)

Combinatorial materials synthesis methods and high-throughput evaluation techniques have been developed to accelerate the process of materials discovery and optimization and phase-diagram mapping. Analogous to integrated circuit chips, integrated materials chips containing thousands of discrete different compositions or continuous phase diagrams, often in the form of high-quality epitaxial thin films, can be fabricated and screened for interesting properties. Microspot x-ray method, various optical measurement techniques, and a novel evanescent microwave microscope have been used to characterize the structural, optical, magnetic, and electrical properties of samples on the materials chips. These techniques are routinely used to discover/optimize and map phase diagrams of ferroelectric, dielectric, optical, magnetic, and superconducting materials.
The surface of Branhamella catarrhalis (1989)

The incidence of B. catarrhalis as a cause of otitis media is increasing. As strategies for preventing infections caused by Streptococcus pneumoniae and nontypable H. influenzae are developed, the relative importance of B. catarrhalis will increase further in the next decade. A goal of studies of surface antigens is to identify potential vaccine components. Surface antigens of B. catarrhalis include OMPs, LOS and fimbriae. Preliminary studies indicate that OMPs and LOS are relatively antigenically conserved among strains. Future investigations should be directed toward identifying conserved antigens that will generate protective antibodies.