Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of P-glycoprotein on flavopiridol sensitivity

Flavopiridol is the first potent inhibitor of cyclin-dependent kinases (CDKs) to enter clinical trials. Little is known about mechanisms of resistance to this agent. In order to determine whether P-glycoprotein (Pgp) might play a role in flavopiridol resistance, we examined flavopiridol sensitivity in a pair of Chinese hamster ovary cell lines differing with respect to level of Pgp expression. The IC50s of flavopiridol in parental AuxB1 (lower Pgp) and colchicine-selected CHRC5 (higher Pgp) cells were 90.2 ± 6.6 nM and 117 ± 2.3 nM, respectively (P< 0.01), suggesting that Pgp might have a modest effect on flavopiridol action. Consistent with this hypothesis, pretreatment with either quinidine or verapamil (inhibitors of Pgp-mediated transport) sensitized CHRC5 cells to the antiproliferative effects of flavopiridol. Because of concern that colony forming assays might not accurately reflect cytotoxicity, we also examined flavopiridol-treated cells by trypan blue staining and flow cytometry. These assays confirmed that flavopiridol was less toxic to cells expressing higher levels of Pgp. Further experiments revealed that flavopiridol inhibited the binding of [3H]-azidopine to Pgp in isolated membrane vesicles, but only at high concentrations. Collectively, these results identify flavopiridol as a weak substrate for Pgp. © 2001 Cancer Research Campaign
Influence of Landscape Elements in Riparian Buffers on the Conservation of Semiaquatic Amphibians

Abstract: Studies on riparian buffers have usually focused on the amount of land needed as habitat for the terrestrial life stages of semiaquatic species. Nevertheless, the landscape surrounding wetlands is also important for other key processes, such as dispersal and the dynamics of metapopulations. Multiple elements that influence these processes should therefore be considered in the delineation of buffers. We analyzed landscape elements (forest cover, density of roads, and hydrographic network) in concentric buffers to evaluate the scale at which they influence stream amphibians in 77 distinct landscapes. To evaluate whether our results could be generalized to other contexts, we determined whether they were consistent across the study areas. Amphibians required buffers of 100–400 m of suitable terrestrial habitat, but interspecific differences in the amount of habitat were large. The presence of amphibians was related to roads and the hydrographic network at larger spatial scales (300–1500 m), which suggests that wider buffers are needed with these elements. This pattern probably arose because these elements influence dispersal and metapopulation persistence, processes that occur at large spatial scales. Furthermore, in some cases, analyses performed on different sets of landscapes provided different results, which suggests caution should be used when conservation recommendations are applied to disparate areas. Establishment of riparian buffers should not be focused only on riparian habitat, but should take a landscape perspective because semiaquatic species use multiple elements for different functions. This approach can be complex because different landscape elements require different spatial extents. Nevertheless, a shift of attention toward the management of different elements at multiple spatial scales is necessary for the long‐term persistence of populations.
Calcium-Induced Calcium Release in Smooth Muscle

Calcium-induced calcium release (CICR) has been observed in cardiac myocytes as elementary calcium release events (calcium sparks) associated with the opening of L-type Ca2+ channels. In heart cells, a tight coupling between the gating of single L-type Ca2+ channels and ryanodine receptors (RYRs) underlies calcium release. Here we demonstrate that L-type Ca2+ channels activate RYRs to produce CICR in smooth muscle cells in the form of Ca2+ sparks and propagated Ca2+ waves. However, unlike CICR in cardiac muscle, RYR channel opening is not tightly linked to the gating of L-type Ca2+ channels. L-type Ca2+ channels can open without triggering Ca2+ sparks and triggered Ca2+ sparks are often observed after channel closure. CICR is a function of the net flux of Ca2+ ions into the cytosol, rather than the single channel amplitude of L-type Ca2+ channels. Moreover, unlike CICR in striated muscle, calcium release is completely eliminated by cytosolic calcium buffering. Thus, L-type Ca2+ channels are loosely coupled to RYR through an increase in global [Ca2+] due to an increase in the effective distance between L-type Ca2+ channels and RYR, resulting in an uncoupling of the obligate relationship that exists in striated muscle between the action potential and calcium release.
Quantitative Proteomics of an Amphibian Pathogen, Batrachochytrium dendrobatidis, following Exposure to Thyroid Hormone

Batrachochytrium dendrobatidis (Bd), a chytrid fungus, has increasingly been implicated as a major factor in the worldwide decline of amphibian populations. The fungus causes chytridiomycosis in susceptible species leading to massive die-offs of adult amphibians. Although Bd infects the keratinized mouthparts of tadpoles and negatively affects foraging behavior, these infections are non-lethal. An important morphogen controlling amphibian metamorphosis is thyroid hormone (T3). Tadpoles may be infected with Bd and the fungus may be exposed to T3 during metamorphosis. We hypothesize that exposure of Bd to T3 may induce the expression of factors associated with host colonization and pathogenicity. We utilized a proteomics approach to better understand the dynamics of the Bd-T3 interaction. Using liquid chromatography-mass spectrometry (LC-MS), we generated a data set of a large number of cytoplasmic and membrane proteins following exposure of Bd to T3. From these data, we identified a total of 263 proteins whose expression was significantly changed following T3 exposure. We provide evidence for expression of an array of proteins that may play key roles in both genomic and non-genomic actions of T3 in Bd. Additionally, our proteomics study shows an increase in several proteins including proteases and a class of uncommon crinkler and crinkler-like effector proteins suggesting their importance in Bd pathogenicity as well as those involved in metabolism and energy transfer, protein fate, transport and stress responses. This approach provides insights into the mechanistic basis of the Bd-amphibian interaction following T3 exposure.
Text-based discovery in biomedicine: the architecture of the DAD-system

Current scientific research takes place in highly specialized contexts with poor communication between disciplines as a likely consequence. Knowledge from one discipline may be useful for the other without researchers knowing it. As scientific publications are a condensation of this knowledge, literature-based discovery tools may help the individual scientist to explore new useful domains. We report on the development of the DAD-system, a concept-based Natural Language Processing system for PubMed citations that provides the biomedical researcher such a tool. We describe the general architecture and illustrate its operation by a simulation of a well-known text-based discovery: The favorable effects of fish oil on patients suffering from Raynaud's disease [1].
Maternal Smoking during Pregnancy and Fetal Organ Growth: A Magnetic Resonance Imaging Study

Objective To study whether maternal cigarette smoking during pregnancy is associated with alterations in the growth of fetal lungs, kidneys, liver, brain, and placenta. Design A case-control study, with operators performing the image analysis blinded. Setting Study performed on a research-dedicated magnetic resonance imaging (MRI) scanner (1.5 T) with participants recruited from a large teaching hospital in the United Kingdom. Participants A total of 26 pregnant women (13 current smokers, 13 non smokers) were recruited; 18 women (10 current smokers, 8 nonsmokers) returned for the second scan later in their pregnancy. Methods Each fetus was scanned with MRI at 22–27 weeks and 33–38 weeks gestational age (GA). Main outcome measures Images obtained with MRI were used to measure volumes of the fetal brain, kidneys, lungs, liver and overall fetal size, as well as placental volumes. Results Exposed fetuses showed lower brain volumes, kidney volumes, and total fetal volumes, with this effect being greater at visit 2 than at visit 1 for brain and kidney volumes, and greater at visit 1 than at visit 2 for total fetal volume. Exposed fetuses also demonstrated lower lung volume and placental volume, and this effect was similar at both visits. No difference was found between the exposed and nonexposed fetuses with regards to liver volume. Conclusion Magnetic resonance imaging has been used to show that maternal smoking is associated with reduced growth of fetal brain, lung and kidney; this effect persists even when the volumes are corrected for maternal education, gestational age, and fetal sex. As expected, the fetuses exposed to maternal smoking are smaller in size. Similarly, placental volumes are smaller in smoking versus nonsmoking pregnant women.
Genetic polymorphisms in inflammatory response genes and their associations with breast cancer risk

Aim To explore the association of NFKB1 c. -798_-795delATTG (rs28362491), NFKBIA c. -949C>T (rs2233406), IL-8 c. -352A>T (rs4073), IL-10 c. -854T>C (rs1800871), TNF c. -418G>A (rs361525), and TNF c. -488G>A (rs1800629) polymorphisms with breast cancer risk in an East Chinese population. Methods We conducted a case-control study including 975 study participants (474 breast cancer patients and 501 female controls without cancer) and genotyped the polymorphisms employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression was used to assess the association of the polymorphisms with breast cancer risk. Results We found that the ins/del and del/del genotypes of NFKB1 polymorphism and TT genotype of IL-10 polymorphism significantly increased breast cancer risk (NFKB1 ins/del odds ratio [OR] 1.69, 95% [CI] 1.23-2.33, P = 0.001; NFKB1 del/del OR 2.42, 95% CI 1.72-3.42, P < 0.001; IL-10 TT OR 2.36, 95% CI 1.58-3.52, P < 0.001). On the other hand, the TT genotype of IL-8 polymorphism, GA and AA genotypes of TNF c. -418G>A polymorphism, and GA genotype of TNF c. -488G>A polymorphism significantly reduced breast cancer risk (IL-8 TT OR 0.48, 95% CI 0.33-0.72, P < 0.001; TNF c.-418 GA OR 0.58, 95% CI 0.41-0.80, P = 0.001; TNF c.-418 AA OR 0.38, 95% CI 0.14-0.98, P = 0.044; TNF c.-488 GA OR 0.68, 95% CI 0.48-0.96, P = 0.029). When stratified by menopausal status, the CT genotype of NFKBIA polymorphism significantly reduced the risk among pre-menopausal women (OR 0.63, 95% CI 0.40-0.99, P = ,043), but not among post-menopausal women. Conclusions NFKB1, NFKBIA, IL-8, IL-10, and TNF polymorphisms could serve as useful predictive biomarkers for breast cancer risk among women in East China.
CP-Miner: A Tool for Finding Copy-paste and Related Bugs in Operating System Code

Copy-pasted code is very common in large software because programmers prefer reusing code via copy-paste in order to reduce programming effort. Recent studies show that copy-paste is prone to introducing bugs and a significant portion of operating system bugs concentrate in copy-pasted code. Unfortunately, it is challenging to efficiently identify copy-pasted code in large software. Existing copy-paste detection tools are either not scalable to large software, or cannot handle small modifications in copy-pasted code. Furthermore, few tools are available to detect copy-paste related bugs. In this paper we propose a tool, CP-Miner, that uses data mining techniques to efficiently identify copy-pasted code in large software including operating systems, and detects copy-paste related bugs. Specifically, it takes less than 20 minutes for CP-Miner to identify 190,000 copy-pasted segments in Linux and 150,000 in FreeBSD. Moreover, CP-Miner has detected 28 copy-paste related bugs in the latest version of Linux and 23 in FreeBSD. In addition, we analyze some interesting characteristics of copy-paste in Linux and FreeBSD, including the distribution of copy-pasted code across different length, granularity, modules, degrees of modification, and various software versions.
Effectiveness of quetiapine for the management of aggressive psychosis in the emergency psychiatric setting: a naturalistic uncontrolled trial

Objective Traditionally, conventional antipsychotics, often administered intramuscularly, are used to reduce hostility and aggression in the emergency setting. This study investigated the efficacy of quetiapine, an oral atypical antipsychotic, in managing aggressive psychosis. Methods Adult hospitalized patients (n=36) with an Overt Aggression Scale (OAS) total score ≥1 and a Brief Psychiatric Rating Scale-derived Psychosis Index score ≥6 received 100–800 mg/day flexibly dosed quetiapine and were monitored daily for a maximum of 5 days. The OAS total score and Physical Aggression Against Others subscale score were primary efficacy assessments. Tolerability was assessed with the Udvalg for Kliniske Undersogelser Side Effects Rating Scale. Results An 83% decrease in the OAS Physical Aggression Against Others subscale score occurred from Day 1 (baseline) to Day 2, which was generally maintained to Day 5; a 39% reduction in OAS total score was observed by Day 2. The OAS total score decreased from a mean baseline of 3.3 to 1.5 at Day 5, a significant decrease for Days 2–4 (P < 0.01) and of borderline significance on Day 5 (P=0.059). Adverse events were mostly mild to moderate with concentration difficulties and somnolence the most common. Conclusion These results from an uncontrolled trial suggest that quetiapine may be helpful for some aggressive patients in the emergency setting.
The relation between multiple sleep latency test findings and the frequency of apneic events in REM and non-REM sleep.

STUDY OBJECTIVES A recent study of 34 patients with mild obstructive sleep apnea syndrome (OSAS) suggested that the number of apneas and hypopneas per hour of sleep (apnea/hypopnea index [AHI]) may show a stronger correlation with sleepiness, as measured by the Multiple Sleep Latency Test (MSLT), when calculated for rapid eye movement (REM) sleep alone (AHIR) as opposed to the entire night. We sought to reexamine this possibility in a larger group of similar patients and in patients who had a wider range of OSAS severity. DESIGN Retrospective and observational. SETTING A large, accredited, academic sleep disorders center where a database of sleep study results is maintained. PATIENTS We studied 1,146 persons who had polysomnography and MSLTs for clinical indications. RESULTS In linear regression models, the AHI explained 11.0% of the variance in MSLT results, AHIN (AHI during non-REM sleep) explained 10.8%, and AHIR explained only 6.0% (p < or = 0.0001 for each). Among subjects with AHI < 10, the AHI explained 3.1% of the variance (p=0.0012), the AHIN 2.3% (p=0.0049), and the AHIR 0.2% (p=0.40). Among all subjects, the ratio AHIR/AHIN had no influence on the overall relationship between AHI and sleepiness (p=0.23). CONCLUSIONS We conclude that apneic events during REM and non-REM sleep probably contribute equally to sleepiness as measured by the MSLT.
CIFAR10-DVS: An Event-Stream Dataset for Object Classification

Neuromorphic vision research requires high-quality and appropriately challenging event-stream datasets to support continuous improvement of algorithms and methods. However, creating event-stream datasets is a time-consuming task, which needs to be recorded using the neuromorphic cameras. Currently, there are limited event-stream datasets available. In this work, by utilizing the popular computer vision dataset CIFAR-10, we converted 10,000 frame-based images into 10,000 event streams using a dynamic vision sensor (DVS), providing an event-stream dataset of intermediate difficulty in 10 different classes, named as “CIFAR10-DVS. ” The conversion of event-stream dataset was implemented by a repeated closed-loop smooth (RCLS) movement of frame-based images. Unlike the conversion of frame-based images by moving the camera, the image movement is more realistic in respect of its practical applications. The repeated closed-loop image movement generates rich local intensity changes in continuous time which are quantized by each pixel of the DVS camera to generate events. Furthermore, a performance benchmark in event-driven object classification is provided based on state-of-the-art classification algorithms. This work provides a large event-stream dataset and an initial benchmark for comparison, which may boost algorithm developments in even-driven pattern recognition and object classification.
Isolated pyogenic pancreatic abscess mimicking a neoplasm.

CONTEXT Pancreatic abscesses are uncommon and usually occur in the setting of pancreatitis. Isolated pyogenic pancreatic abscesses without any precipitating events are extremely rare. CASE REPORT A 72-year-old man with a two month history of non-specific abdominal discomfort, distension, anorexia and weight loss was admitted for further evaluation. A computer tomography scan showed a lesion of the pancreatic head suspicious for a malignancy. Unexpectedly, Klebsialla pneumoniae was isolated from the aspiration biopsy without any evidence of malignancy. A repeat CT scan four months later showed resolution of the abscess after a six week course of antibiotic. CONCLUSION Our case highlights a rare case of isolated pyogenic pancreatic abscess secondary to Klebsialla pneumoniae mimicking an underlying pancreatic malignancy. Infective causes should be considered to avoid any unnecessary major surgery.
Prediction of dissolution-absorption relationships from a continuous dissolution/Caco-2 system

The objectives were 1) to design a continuous dissolution Caco-2 system to predict the dissolution-absorption relationships for fast and slow dissolving formulations of piroxicam, metoprolol tartrate, and ranitidine HCl, and compare the predicted relationships with observed relationships from clinical studies; 2) to estimate the effect of croscarmellose sodium on ranitidine dissolution-absorption relationships; and 3) to estimate the effect of solubilizing agents on piroxicam dissolution-absorption relationships. A continuous dissolution/Caco-2 system was constructed from a dissolution apparatus and a diffusion cell, such that drug dissolution and permeation across a Caco-2 monolayer would occur sequentially and simultaneously. The continuous system generally matched observed dissolution-absorption relationships from clinical studies. For example, the system successfully predicted the slow metoprolol and slow ranitidiine formulations to be permeation-rate-limited. The system predicted the slow piroxicam formulation to be dissolution-rate-limited, and the fast piroxicam formulation to be permeation-rate-limited, in spite of piroxicam’s high permeability and low solubility. Additionally, the system indicated croscarmellose sodium enhanced ranitidine permeability and predicted solubilizing agents to not modulate permeability. These results suggest a dissolution/Caco-2 system to be an experimentally based tool that may predict dissolution-absorption relationships from oral solid dosage forms, and hence the relative contributions of dissolution and permeation to oral drug absorption kinetics.
Analysis and design of a 30 MHz resonant boost converter

This paper presents the analysis and design procedure of a Zero Voltage Switching (ZVS) resonant Boost converter operating at 30 MHz under hysteretic control (also called on-off control or bang-bang control). The Boost converter is based on the Class Φ inverter and combined with a class E rectifier. A multi-stage resonant gate driver is used to drive the power MOSFET effectively. The power train, gate dive and control design are provided in detail respectively. The design considerations are presented based on the efficiency optimization between the high component stress and the effect of parasitic parameters. The simulation results of the 30 MHz resonant Boost converter are given to verify the validity of the design method. An experimental prototype is being built.
Protective Effect of Total Phenolic Compounds from Inula helenium on Hydrogen Peroxide-induced Oxidative Stress in SH-SY5Y Cells

Inula helenium has been reported to contain a large amount of phenolic compounds, which have shown promise in scavenging free radicals and prevention of neurodegenerative diseases. This study is to investigate the neuroprotective effects of total phenolic compounds from I. helenium on hydrogen peroxide-induced oxidative damage in human SH-SY5Y cells. Antioxidant capacity of total phenolic compounds was determined by radical scavenging activity, the level of intracellular reactive oxygen species and superoxide dismutase activity. The cytotoxicity of total phenolic compounds was determined using a cell counting kit-8 assay. The effect of total phenolic compounds on cell apoptosis due to hydrogen peroxide-induced oxidative damage was detected by Hoechst 33258 and Annexin-V/PI staining using fluorescence microscope and flow cytometry, respectively. Mitochondrial function was evaluated using the mitochondrial membrane potential and mitochondrial ATP synthesis by JC-1 dye and high performance liquid chromatography, respectively. It was shown that hydrogen peroxide significantly induced the loss of cell viability, increment of apoptosis, formation of reactive oxygen species, reduction of superoxide dismutase activity, decrease in mitochondrial membrane potential and a decrease in adenosine triphosphate production. On the other hand, total phenolic compounds dose-dependently reversed these effects. This study suggests that total phenolic compounds exert neuroprotective effects against hydrogen peroxide-induced oxidative damage via blocking reactive oxygen species production and improving mitochondrial function. The potential of total phenolic compounds and its neuroprotective mechanisms in attenuating hydrogen peroxide-induced oxidative stress-related cytotoxicity is worth further exploration.
Regulation of Lens Fiber Cell Differentiation by Transcription Factor c-Maf*

To elucidate the regulatory mechanisms underlying lens development, we searched for members of the large Maf family, which are expressed in the mouse lens, and found three, c-Maf, MafB, and Nrl. Of these, the earliest factor expressed in the lens was c-Maf. The expression of c-Maf was most prominent in lens fiber cells and persisted throughout lens development. To examine the functional contribution of c-Maf to lens development, we isolated genomic clones encompassing the murine c-maf gene and carried out its targeted disruption. Insertion of the β-galactosidase (lacZ) gene into the c-maf locus allowed visualization of c-Maf accumulation in heterozygous mutant mice by staining for LacZ activity. Homozygous mutant embryos and newborns lacked normal lenses. Histological examination of these mice revealed defective differentiation of lens fiber cells. The expression of crystallin genes was severely impaired in the c-maf-null mutant mouse lens. These results demonstrate that c-Maf is an indispensable regulator of lens differentiation during murine development.