gebhart/patrepeval huggingface dataset:
Deleterious Effects of Neonicotinoid Pesticides on Drosophila melanogaster Immune Pathways (2019)

Neonicotinoid insecticides are common agrochemicals that are used to kill pest insects and improve crop yield. However, sublethal exposure can exert unintentional toxicity to honey bees and other beneficial pollinators by dysregulating innate immunity. Generation of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) by the dual oxidase (Duox) pathway is a critical component of the innate immune response, which functions to impede infection and maintain homeostatic regulation of the gut microbiota. Despite the importance of this pathway in gut immunity, the consequences of neonicotinoid exposure on Duox signaling have yet to be studied. Here, we use a <i>Drosophila melanogaster</i> model to investigate the hypothesis that imidacloprid (a common neonicotinoid) can affect the Duox pathway. The results demonstrated that exposure to sublethal imidacloprid reduced H<sub>2</sub>O<sub>2</sub> production by inhibiting transcription of the <i>Duox</i> gene. Furthermore, the reduction in <i>Duox</i> expression was found to be a result of imidacloprid interacting with the midgut portion of the immune deficiency pathway. This impairment led to a loss of microbial regulation, as exemplified by a compositional shift and increased total abundance of <i>Lactobacillus</i> and <i>Acetobacter</i> spp. (dominant microbiota members) found in the gut. In addition, we demonstrated that certain probiotic lactobacilli could ameliorate Duox pathway impairment caused by imidacloprid, but this effect was not directly dependent on the Duox pathway itself. This study is the first to demonstrate the deleterious effects that neonicotinoids can have on Duox-mediated generation of H<sub>2</sub>O<sub>2</sub> and highlights a novel coordination between two important innate immune pathways present in insects.<b>IMPORTANCE</b> Sublethal exposure to certain pesticides (e.g., neonicotinoid insecticides) is suspected to contribute to honey bee (<i>Apis mellifera</i>) population decline in North America. Neonicotinoids are known to interfere with immune pathways in the gut of insects, but the underlying mechanisms remain elusive. We used a <i>Drosophila melanogaster</i> model to understand how imidacloprid (a common neonicotinoid) interferes with two innate immune pathways-Duox and Imd. We found that imidacloprid dysregulates these pathways to reduce hydrogen peroxide production, ultimately leading to a dysbiotic shift in the gut microbiota. Intriguingly, we found that presupplementation with probiotic bacteria could mitigate the harmful effects of imidacloprid. Thus, these observations uncover a novel mechanism of pesticide-induced immunosuppression that exploits the interconnectedness of two important insect immune pathways.
High-mobility carbon-nanotube thin-film transistors on a polymeric substrate (2005)

We report the development of high-mobility carbon-nanotube thin-film transistors fabricated on a polymeric substrate. The active semiconducting channel in the devices is composed of a random two-dimensional network of single-walled carbon nanotubes (SWNTs). The devices exhibit a field-effect mobility of 150cm2∕Vs and a normalized transconductance of 0.5mS∕mm. The ratio of on-current (Ion) to off-current (Ioff) is ∼100 and is limited by metallic SWNTs in the network. With electronic purification of the SWNTs and improved gate capacitance we project that the transconductance can be increased to ∼10–100mS∕mm with a significantly higher value of Ion∕Ioff, thus approaching crystalline semiconductor-like performance on polymeric substrates.
Nitric Oxide Scavenging by Red Blood Cells as a Function of Hematocrit and Oxygenation (2005)

The reaction rate between nitric oxide and intraerythrocytic hemoglobin plays a major role in nitric oxide bioavailability and modulates homeostatic vascular function. It has previously been demonstrated that the encapsulation of hemoglobin in red blood cells restricts its ability to scavenge nitric oxide. This effect has been attributed to either factors intrinsic to the red blood cell such as a physical membrane barrier or factors external to the red blood cell such as the formation of an unstirred layer around the cell. We have performed measurements of the uptake rate of nitric oxide by red blood cells under oxygenated and deoxygenated conditions at different hematocrit percentages. Our studies include stopped-flow measurements where both the unstirred layer and physical barrier potentially participate, as well as competition experiments where the potential contribution of the unstirred layer is limited. We find that deoxygenated erythrocytes scavenge nitric oxide faster than oxygenated cells and that the rate of nitric oxide scavenging for oxygenated red blood cells increases as the hematocrit is raised from 15% to 50%. Our results 1) confirm the critical biological phenomenon that hemoglobin compartmentalization within the erythrocyte reduces reaction rates with nitric oxide, 2) show that extra-erythocytic diffusional barriers mediate most of this effect, and 3) provide novel evidence that an oxygen-dependent intrinsic property of the red blood cell contributes to this barrier activity, albeit to a lesser extent. These observations may have important physiological implications within the microvasculature and for pathophysiological disruption of nitric oxide homeostasis in diseases.
Tumour Necrosis Factor: Strategies for Improving the Therapeutic Index (1998)

Tumour Necrosis Factor (TNF) is a cytokine initially discovered for its capacity to induce haemorrhagic necrosis of experimental tumours and later found to be endowed with potent proinflammatory activities. It was soon realised that these latter properties were at the origin of unacceptable systemic toxicity in all trials aimed at exploiting the anti-tumour activities of TNF. The present review intends to reconsider the efforts that have been devoted over the past ten years to increase the therapeutic index of TNF so to make it a useful drug for the treatment of malignancies. Overall, attempts to achieve this goal with systemically administered TNF have met little success so far. On the other hand, impressive results have been obtained with locoregional administration of TNF. Although of relatively limited clinical utility, these observations have indicated a realistic possibility for a therapeutic exploitation of TNF in tumour therapy: the delivery of systemically administered TNF to the site of tumour growth. On this basis, different targeting and pre-targeting strategies have been developed to achieve this goal. While still in their infancy, these approaches have yielded encouraging results in experimental tumour models. In the forthcoming years it will be possible to evaluate if they represent a practicable means of delivering high doses of TNF to the tumour while sparing the organism from systemic, toxic effects.
ERK Kinase Inhibition Stabilizes the Aryl Hydrocarbon Receptor (2004)

The ultimate carcinogen and metabolite of benzo-[a]pyrene-7,8-dihydrodiol, benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (+/-), stimulates apoptosis, and this process can be blocked by extracellular signal-regulated kinase (Erk) kinase inhibitors. However, we show here that Erk kinase inhibitors were unable to prevent B[a]P-7,8-dihydrodiol-induced apoptosis, leading us to speculate that Erk kinases are linked to regulation of the aryl hydrocarbon (Ah) receptor. Cotreatment of hepa1c1c7 cells with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and Erk kinase inhibitor PD98059, U0126, or SL327 led to enhanced nuclear accumulation of Ah receptor but with a reduced capacity to complement TCDD induction of Cyp1a1. This is explained in part by the ability of Erk kinase inhibitors to alter the steady-state levels of cellular Ah receptor, a result that leads to a dramatic induction in detectable receptor levels. These changes in cellular Ah receptor levels are associated with delayed degradation of the Ah receptor because TCDD-initiated degradation is reversed when cells are co-treated with TCDD and Erk kinase inhibitors. Erk kinase is linked to Ah receptor expression, as demonstrated by reductions in total Ah receptor levels after overexpression of constitutively active MEK1. In addition, Erk kinase activity modulates the transcriptional response because MEK1 overexpression enhances TCDD-initiated transactivation potential of the receptor. Thus, Erk kinase activity facilitates ligand-initiated transcriptional activation while targeting the Ah receptor for degradation. Immunoprecipitation experiments of the Ah receptor indicate that Erk kinase activity is associated with the receptor. It is interesting that the carboxyl region of the Ah receptor is associated with the transactivation region as well as the site for ubiquitination, indicating that Erk kinase-dependent phosphorylation targets the carboxyl region of the receptor.
Prevention of Cardiovascular Disease (2012)

This chapter contains sections titled: Introduction Cardiovascular disease: etiology and assessment Landmark studies of cardiovascular disease risk Key risk factors Risk assessment Population-based prevention Clinical trials that have informed our management of preventing CAD and other vascular diseases Update References
One-Month Prevalence of Mental Disorders in the United States (1988)

One-month prevalence results were determined from 18,571 persons interviewed in the first-wave community samples of all five sites that constituted the National Institute of Mental Health Epidemiologic Catchment Area Program. US population estimates, based on combined site data, were that 15.4% of the population 18 years of age and over fulfilled criteria for at least one alcohol, drug abuse, or other mental disorder during the period one month before interview. Higher prevalence rates of most mental disorders were found among younger people (less than age 45 years), with the exception of severe cognitive impairments. Men had higher rates of substance abuse and antisocial personality, whereas women had higher rates of affective, anxiety, and somatization disorders. When restricted to the diagnostic categories covered in international studies based on the Present State Examination, results fell within the range reported for European and Australian studies.
Road Boundary Detection For Autonomous Vehicle Navigation (1986)

The Computer Vision Laboratory at the University of Maryland for the past year has been developing a computer vision system for autonomous ground navigation of roads and road networks for the Defense Advanced Research Projects Agency's Strategic Computing Program. The complete system runs on a VAX 11/785, but certain parts of it have been reimplemented on a VICOM image processing system for experimentation on an autonomous vehicle built for the Martin Marietta Corp., Aerospace Division, in Denver, Colorado. We give a brief overview of the principal software components of the system and then describe the VICOM implementation in detail.
Expression of 25-Hydroxyvitamin D3-24-Hydroxylase Activity in Caco-2 Cells, Anin VitroModel of Intestinal Vitamin D Catabolism* (1990)

The C-24 oxidation pathway plays a major role in the degradation of vitamin D metabolites in kidney and other target tissues. The aim of the present study was to establish an intestinal cell culture system to study the mechanisms regulating the vitamin D catabolic pathway. 25-Hydroxyvitamin D3-24-hydroxylase (24-hydroxylase), the first enzyme in the catabolic sequence, was examined in Caco-2 cells, a human colon adenocarcinoma cell line which exhibits differentiated functions of absorbing intestinal epithelial cells. While untreated Caco-2 cells did not exhibit 24-hydroxylase activity, significant catabolic activity was induced by prior treatment of cell monolayers with 1,25-dihydroxyvitamin D3(1,25-(OH)2D3). Induced 24-hydroxylase D3 (25OHD3) and 1,25-(OH)2D3 was detected 6 h after treatment of cells with 10(-8)M 1,25-(OH)2D3, peaked at 16 h, and decreased thereafter. Treatment of cells with 10(-7) M 1,25-(OH)2D3 elicited a maximal 24-hydroxylase response. Comparable time courses of induction by 1,25-(OH)2D3 and 1,25-(OH)2D3-dose response curves were observed in cultured human skin fibroblasts and Caco-2 cells. 25OHD3 was not as good an inducer of the vitamin D catabolic pathway in Caco-2 cells as 1,25-(OH)2D3. Induction of 24-hydroxylase activity by 1,25-(OH)2D3 was inhibited by pretreatment of Caco-2 cells with either actinomycin D, alpha-amanitin, or cycloheximide suggesting that mRNA and protein synthesis are required for induction. The present study demonstrates that 1,25-(OH)2D3-treated Caco-2 cells express the vitamin D catabolic pathway and, therefore, constitute a useful in vitro model to study the mechanism of induction by 1,25-(OH)2D3.
Cutting Edge: CD1d Deficiency Impairs Murine Host Defense Against the Spirochete, Borrelia burgdorferi (2000)

CD1 molecules can present microbial lipid Ag to T cells, suggesting that they participate in host defense against pathogens. In this study, we examined the role of CD1d in resistance to infection with the Lyme disease spirochete, Borrelia burgdorferi (Bb), an organism with proinflammatory lipid Ag. Bb infection of CD1d-deficient (CD1d(-/-)) mouse strains normally resistant to this pathogen resulted in arthritis. Pathology correlated with an increased prevalence of spirochete DNA in tissues and enhanced production of Bb-specific IgG, including IgG to Ag rapidly down-modulated on spirochetes in vivo. CD1d(-/-) mice exhibited high-titer Bb-specific IgG2a, an isotype commonly induced in disease-susceptible mice but not in the disease-resistant control mice in this study. These results show that CD1d deficiency impairs host resistance to a spirochete pathogen, and are the first example of a mutation that imparts Bb-resistant mice with the Ab and disease profile of a susceptible mouse strain.
Effects of piperine, the pungent component of black pepper, at the human vanilloid receptor (TRPV1) (2005)

1. We have characterised the effects of piperine, a pungent alkaloid found in black pepper, on the human vanilloid receptor TRPV1 using whole-cell patch-clamp electrophysiology. 2. Piperine produced a clear agonist activity at the human TRPV1 receptor yielding rapidly activating whole-cell currents that were antagonised by the competitive TRPV1 antagonist capsazepine and the non-competitive TRPV1 blocker ruthenium red. 3. The current-voltage relationship of piperine-activated currents showed pronounced outward rectification (25+/-4-fold between -70 and +70 mV) and a reversal potential of 0.0+/-0.4 mV, which was indistinguishable from that of the prototypical TRPV1 agonist capsaicin. 4. Although piperine was a less potent agonist (EC50=37.9+/-1.9 microM) than capsaicin (EC50=0.29+/-0.05 microM), it demonstrated a much greater efficacy (approximately two-fold) at TRPV1. 5. This difference in efficacy did not appear to be related to the proton-mediated regulation of the receptor since a similar degree of potentiation was observed for responses evoked by piperine (230+/-20%, n=11) or capsaicin (284+/-32%, n=8) upon acidification to pH 6.5. 6. The effects of piperine upon receptor desensitisation were also unable to explain this effect since piperine resulted in more pronounced macroscopic desensitisation (t(1/2)=9.9+/-0.7 s) than capsaicin (t(1/2)>20 s) and also caused greater tachyphylaxis in response to repetitive agonist applications. 7. Overall, our data suggest that the effects of piperine at human TRPV1 are similar to those of capsaicin except for its propensity to induce greater receptor desensitisation and, rather remarkably, exhibit a greater efficacy than capsaicin itself. These results may provide insight into the TRPV1-mediated effects of piperine on gastrointestinal function.
Quantum dynamics of single trapped ions (2003)

Single trapped ions represent elementary quantum systems that are well isolated from the environment. They can be brought nearly to rest by laser cooling, and both their internal electronic states and external motion can be coupled to and manipulated by light fields. This makes them ideally suited for quantum-optical and quantum-dynamical studies under well-controlled conditions. Theoretical and experimental work on these topics is reviewed in the paper, with a focus on ions trapped in radio-frequency (Paul) traps.
Molecular Markers of Early Pancreatic Cancer (2005)

Pancreatic cancer is a deadly disease and the fourth most common cause of cancer death in the United States. Since chemotherapy and radiotherapy have thus far largely failed to significantly improve the survival of patients with pancreatic ductal adenocarcinoma, there is considerable interest in identifying better diagnostic markers of pancreatic neoplasia. Not only could better markers improve the early diagnosis of pancreatic cancer and allow more patients to undergo curative surgical resection, but also could potentially be used for patients at high risk of developing pancreatic cancer to identify precancerous lesions while they are amenable to cure. A wealth of information has recently become available about gene expression, DNA methylation, and proteomics alterations that occur in pancreatic cancers creating hope that better diagnostic markers of pancreatic cancer will be soon forthcoming.
Thermostable DNA Ligase-Mediated PCR Production of Circular Plasmid (PPCP) and Its Application in Directed Evolution via In situ Error-Prone PCR (2013)

Polymerase chain reaction (PCR) is a powerful method to produce linear DNA fragments. Here we describe the Tma thermostable DNA ligase-mediated PCR production of circular plasmid (PPCP) and its application in directed evolution via in situ error-prone PCR. In this thermostable DNA ligase-mediated whole-plasmid amplification method, the resultant DNA nick between the 5' end of the PCR primer and the extended newly synthesized DNA 3' end of each PCR cycle is ligated by Tma DNA ligase, resulting in circular plasmid DNA product that can be directly transformed. The template plasmid DNA is eliminated by 'selection marker swapping' upon transformation. When performed under an error-prone condition with Taq DNA polymerase, PPCP allows one-step construction of mutagenesis libraries based on in situ error-prone PCR so that random mutations are introduced into the target gene without altering the expression vector plasmid. A significant difference between PPCP and previously published methods is that PPCP allows exponential amplification of circular DNA. We used this method to create random mutagenesis libraries of a xylanase gene and two cellulase genes. Screening of these libraries resulted in mutant proteins with desired properties, demonstrating the usefulness of in situ error-prone PPCP for creating random mutagenesis libraries for directed evolution.
Identification of genes associated with metastasis of mammary carcinoma in metastatic versus non-metastatic cell lines. (2002)

Cell lines 4A4 and 2C5 are the respective metastatic and non-metastatic variants (nude mouse system) derived from the human mammary carcinoma cell line MDA-MB-435. In order to identify genes associated with or functionally involved in metastasis, we have extended our previous transcriptional profile from 5000 to 12,000 genes using the Affymetrix Gene Chip array technology. Based on a threshold level of a change factor of > or = 2.5, we found that the steady-state level of 40 genes (0.3%) was up-regulated and conversely 89 genes (0.7%) were down-regulated in the metastatic cell line 4A4. The de-regulated genes were classified into categories such as tumor antigens/transmembrane receptors, enzymes, mediators of signaling, cell migration and angiogenesis, cell-cycle-, apoptosis-, differentiation- and growth-factor related genes, tumor suppression, transcription factors and genes encoding components of the extracellular matrix and the cytoskeleton. As possible mediators of invasion we identified DGCR6, osteopontin, autotaxin and the 65 kD phosphoprotein p65. In addition, three sugar-modifying enzymes were up-regulated in cell line 4A4. Profound differences in G-protein-mediated signaling and down-regulation of the tumor-suppressor genes DPC4, BARDI and DLC-1 were noted in the metastatic cell line 4A4.
The evolution of IBM CMOS DRAM technology (1995)

The development of DRAM at IBM produced many novel processes and sophisticated analysis methods. Improvements in lithography and innovative process features reduced the cell size by a factor of 18.8 in the time between the 4Mb and 256Mb generations. The original substrate plate trench cell used in the 4Mb chip is still the basis of the 256Mb technology being developed today. This paper describes some of the more important and interesting innovations introduced in IBM CMOS DRAMs. Among them, shallow-trench isolation, I-line and deep-UV (DUV) lithography, titanium salicidation, tungsten stud contacts, retrograde n-well, and planarized back-end-of-line (BEOL) technology are core elements of current state-of-the-art logic technology described in other papers in this issue. The DRAM specific features described are borderless contacts, the trench capacitor, trench-isolated cell devices, and the “strap.” Finally, the methods for study and control of leakage mechanisms which degrade DRAM retention time are described.
End-Tidal CO2 Pressure and Cardiac Performance during Exercise in Heart Failure (2008)

Reduced PetCO2 reflects impairments in the functional, ventilatory, and cardiac performance response to exercise in patients with HF. PetCO2 can supplement other clinical and CPX indices in the functional and prognostic evaluation of patients with HF.
A switch from Myc:Max to Mad:Max heterocomplexes accompanies monocyte/macrophage differentiation. (1993)

Mad is a basic-helix-loop-helix-zipper protein that heterodimerizes with Max in vitro. Mad:Max heterodimers recognize the same E-box-related DNA-binding sites as Myc:Max heterodimers. However, in transient transfection assays Myc and Mad influence transcription in opposite ways through interaction with Max; Myc activates while Mad represses transcription. Here, we demonstrate that Mad protein is induced rapidly upon differentiation of cells of the myeloid lineage. The Mad protein is synthesized in human cells as a 35-kD nuclear phosphoprotein with an extremely short half-life (t1/2 = 15-30 min) and can be detected in vivo in a complex with Max. In the undifferentiated U937 monocyte cell line Max was found complexed with Myc but not Mad. However, Mad:Max complexes began to accumulate as early as 2 hr after induction of macrophage differentiation with TPA. By 48 hr following TPA treatment only Mad:Max complexes were detectable. These data show that differentiation is accompanied by a change in the composition of Max heterocomplexes. We speculate that this switch in heterocomplexes results in a change in the transcriptional regulation of Myc:Max target genes required for cell proliferation.