Miracle-dz/UniFAR-FTUs huggingface dataset:
Lactation Stage Influences Drug Milk-to-Serum Values and Neonatal Exposure Risk

The purpose of our study was to assess the influence of lactation stage–dependent differences in milk-to-serum (M/S) ratio for an actively transported drug (cefepime) on the calculation of 2 exposure indices, EIDose and EIConc. Age-dependent differences in cefepime pharmacokinetics at postnatal days 4 and 10 as well as cefepime M/S values at lactation days 4 and 10 in rats were determined. Significantly higher elimination rate constant and systemic clearance and lower half-life were found in day 10 compared to day 4 pups with no differences in oral bioavailability. The EIConc was quantitatively higher than EIDose at both lactation stages. The ~7-fold decrease in cefepime M/S values at lactation day 10 resulted in ~7-fold reduction in the EIDose and ~13-fold reduction in EIConc. Our study confirms the need to evaluate M/S at different lactation stages for actively transported drugs to avoid over- or underestimation of neonatal exposure risk.
The San Francisco Renaissance: Poetics and Community at Mid-Century

Preface Acknowledgments Introduction: enabling fictions 1. The elegiac mode: rhetoric and poetics in the 1940s 2. 'The darkness surrounds us': participation and reflection among the beat writers 3. 'Spotting that design': incarnation and interpretation in Gary Snyder and Philip Whalen 4. 'Cave of resemblances, cave of Rimes': tradition and repetition in Robert Duncan 5. The city redefined: community and dialogue in Jack Spicer 6. Appropriations: women and the San Francisco renaissance 7. Approaching the fin de siecle Notes Index.
Computing Safe Contention Bounds for Multicore Resources with Round-Robin and FIFO Arbitration

Numerous researchers have studied the contention that arises among tasks running in parallel on a multicore processor. Most of those studies seek to derive a tight and sound upper-bound for the worst-case delay with which a processor resource may serve an incoming request, when its access is arbitrated using time-predictable policies such as round-robin or FIFO. We call this value <italic>upper-bound delay</italic> (<inline-formula> <tex-math notation="LaTeX">$ubd$</tex-math><alternatives> <inline-graphic xlink:href="fernandez-ieq1-2616307.gif"/></alternatives></inline-formula>). Deriving trustworthy <inline-formula><tex-math notation="LaTeX">$ubd$</tex-math><alternatives> <inline-graphic xlink:href="fernandez-ieq2-2616307.gif"/></alternatives></inline-formula> statically is possible when sufficient public information exists on the timing latency incurred on access to the resource of interest. Unfortunately however, that is rarely granted for commercial-of-the-shelf (COTS) processors. Therefore, the users resort to measurement observations on the target processor and thus compute a “measured” <inline-formula> <tex-math notation="LaTeX">$ubd_{m}$</tex-math><alternatives> <inline-graphic xlink:href="fernandez-ieq3-2616307.gif"/></alternatives></inline-formula>. However, using <inline-formula><tex-math notation="LaTeX">$ubd_{m}$</tex-math><alternatives> <inline-graphic xlink:href="fernandez-ieq4-2616307.gif"/></alternatives></inline-formula> to compute worst-case execution time values for programs running on COTS multicore processors requires qualification on the soundness of the result. In this paper, we present a measurement-based methodology to derive a <inline-formula> <tex-math notation="LaTeX">$ubd_m$</tex-math><alternatives> <inline-graphic xlink:href="fernandez-ieq5-2616307.gif"/></alternatives></inline-formula> under <italic>round-robin </italic> (RoRo) and <italic>first-in-first-out</italic> (FIFO) arbitration, which accurately approximates <inline-formula><tex-math notation="LaTeX">$ubd$</tex-math><alternatives> <inline-graphic xlink:href="fernandez-ieq6-2616307.gif"/></alternatives></inline-formula> from above, without needing latency information from the hardware provider. Experimental results, obtained on multiple processor configurations, demonstrate the robustness of the proposed methodology.
Alcohol Use Predicts ER Visits in Individuals with Alpha-1 Antitrypsin Deficiency (AATD) Associated COPD

Abstract Excessive alcohol use in COPD has been associated with increased mortality; however, little is known about alcohol use in AATD-associated COPD. A total of 538 individuals with AATD-associated COPD completed questionnaires at baseline and 330 also completed 2 years of follow-up questionnaires. Demographic and health information was collected, including information about alcohol use, ER visits for COPD, and hospitalizations for COPD. Problem alcohol use was characterized using the CAGE screening questionnaire and recent alcohol consumption. Demographic and clinical characteristics associated with problem drinking were identified using logistic regression. Problem drinking at baseline was examined as a predictor of ER visits and hospital admissions for COPD in the subsequent two years using logistic regression adjusting for demographic variables and baseline health status. 14% of the sample reported a history of problem drinking per the CAGE and 8% reported problem drinking in the past week. Problem drinking was associated with higher education and greater lifetime tobacco exposure. Recent alcohol consumption was a significant predictor of having an ER visit for COPD in the subsequent two years. Compared to individuals who reported problem drinking in the past week, individuals with no consumption (OR = 0.32, 95% CI = 0.10 to 0.97, p = .043) and individuals with low-to-moderate consumption (OR = 0.25, 95% CI = 0.08 to 0.77, p = .016) had significantly lower odds of an ER visit. Neither measure of problem drinking predicted hospital admission. Screening for recent excessive alcohol use in this population may identify individuals at risk for use of costly emergency health services.
Nuclear LC3 Associates with Slowly Diffusing Complexes that Survey the Nucleolus

MAP1LC3B (microtubule‐associated protein 1 light chain 3, LC3) is a key component of the autophagy pathway, contributing to both cargo selection and autophagosome formation in the cytoplasm. Emerging evidence suggests that nuclear forms of LC3 are also functionally important; however, the mechanisms that facilitate the nuclear targeting and trafficking of LC3 between the nucleus and cytoplasm under steady‐state conditions are poorly understood. In this study, we examine how residues known to regulate the interactions between LC3 and other proteins or RNA (F52 L53, R68‐R70 and G120) contribute to its nuclear targeting, nucleocytoplasmic transport and association with nucleoli and other nuclear components. We find that residues F52 L53 and R68‐70, but not G120, regulate targeting of LC3 to the nucleus, its rates of nucleocytoplasmic transport and the apparent sizes of LC3‐associated complexes in the nucleus inferred from fluorescence recovery after photobleaching (FRAP) measurements. We also show that LC3 is enriched in nucleoli and its triple arginine motif is especially important for nucleolar targeting. Finally, we identify a series of candidate nuclear LC3‐interacting proteins using mass spectrometry, including MAP1B, tubulin and several 40S ribosomal proteins. These findings suggest LC3 is retained in the nucleus in association with high‐molecular weight complexes that continuously scan the nucleolus.
TLR8, but not TLR7, induces the priming of the NADPH oxidase activation in human neutrophils

Neutrophils play a key role in host defense against invading pathogens by releasing toxic agents, such as ROS and antimicrobial peptides. Human neutrophils express several TLRs that recognize a variety of microbial motifs. The interaction between TLR and their agonists is believed to help neutrophils to recognize and to kill pathogens efficiently by increasing their activation, a process called priming. However, excessive activation can induce tissue injury and thereby, contribute to inflammatory disorders. Agonists that activate TLR7 and TLR8 induce priming of neutrophil ROS production; however, which receptor is involved in this process has not been elucidated. In this study, we show that the selective TLR8 agonist, CL075 (3M002), induced a dramatic increase of fMLF‐stimulated NOX2 activation, whereas the selective TLR7 agonist, loxoribine, failed to induce any priming effect. Interestingly, CL075, but not loxoribine, induced the phosphorylation of the NOX2 cytosolic component p47phox on several serines and the phosphorylation of p38MAPK and ERK1/2. The inhibitor of p38MAPK completely blocked CL075‐induced phosphorylation of p47phox Ser345. Moreover, CL075, but not loxoribine, induced the activation of the proline isomerase Pin1, and juglone, a Pin1 inhibitor, prevented CL075‐mediated priming of fMLF‐induced superoxide production. These results indicate that TLR8, but not TLR7, is involved in priming of human neutrophil ROS production by inducing the phosphorylation of p47phox and p38MAPK and that Pin1 is also involved in this process.
Expression of calcineurin and its interacting proteins in epileptic fowl

Calcineurin (CaN), a Ca2+–calmodulin (CaM)‐dependent protein phosphatase, is important for Ca2+‐mediated signal transduction. The main objective of this study was to examine the potential role of CaN in epileptic brain and its involvement in neuronal apoptosis. We investigated CaN expression and its interaction with various signaling molecules in normal, carrier and epileptic brain tissues of chicken. Our results revealed higher Ca2+–CaM‐dependent phosphatase activity of CaN and a correspondingly strong immunoreactive band of CaN A in epileptic and carrier brain samples compared with normal brain. Furthermore, immunohistochemical analysis showed a higher level of expression of CaN in epileptic brain tissue. However, the intensity of immunoreactivity was less in carrier than epileptic brain. We observed that the interaction of CaN with m‐calpain and µ‐calpain was strong in carrier and epileptic chickens compared with that in normal birds. In addition, the interaction of CaN with Bcl‐2, caspase‐3 and p53 was greater in carrier and epileptic fowl than in normal chickens. The greater interaction of CaN with various apoptotic factors in epileptic chickens adds to our understanding of the mechanism of CaN signaling in neuronal apoptosis.
Total testosterone assays in women with polycystic ovary syndrome: precision and correlation with hirsutism.

CONTEXT There is no standardized assay of testosterone in women. Liquid chromatography mass spectrometry (LC/MS) has been proposed as the preferable assay by an Endocrine Society Position Statement. OBJECTIVE The aim was to compare assay results from a direct RIA with two LC/MS. DESIGN AND SETTING We conducted a blinded laboratory study including masked duplicate samples at three laboratories--two academic (University of Virginia, RIA; and Mayo Clinic, LC/MS) and one commercial (Quest, LC/MS). PARTICIPANTS AND INTERVENTIONS Baseline testosterone levels from 596 women with PCOS who participated in a large, multicenter, randomized controlled infertility trial performed at academic health centers in the United States were run by varying assays, and results were compared. MAIN OUTCOME MEASURE We measured assay precision and correlation and baseline Ferriman-Gallwey hirsutism scores. RESULTS Median testosterone levels were highest with RIA. The correlations between the blinded samples that were run in duplicate were comparable. The correlation coefficient (CC) between LC/MS at Quest and Mayo was 0.83 [95% confidence interval (CI), 0.80-0.85], between RIA and LC/MS at Mayo was 0.79 (95% CI, 0.76-0.82), and between RIA and LC/MS at Quest was 0.67 (95% CI, 0.63-0.72). Interassay variation was highest at the lower levels of total testosterone (≤50 ng/dl). The CC for Quest LC/MS was significantly different from those derived from the other assays. We found similar correlations between total testosterone levels and hirsutism score with the RIA (CC=0.24), LC/MS at Mayo (CC=0.15), or Quest (CC=0.17). CONCLUSIONS A testosterone RIA is comparable to LC/MS assays. There is significant variability between LC/MS assays and poor precision with all assays at low testosterone levels.
Linking contemporary high resolution magnetic resonance imaging to the von economo legacy: A study on the comparison of MRI cortical thickness and histological measurements of cortical structure

The cerebral cortex is a distinctive part of the mammalian nervous system, displaying a spatial variety in cyto‐, chemico‐, and myelinoarchitecture. As part of a rich history of histological findings, pioneering anatomists von Economo and Koskinas provided detailed mappings on the cellular structure of the human cortex, reporting on quantitative aspects of cytoarchitecture of cortical areas. Current day investigations into the structure of human cortex have embraced technological advances in Magnetic Resonance Imaging (MRI) to assess macroscale thickness and organization of the cortical mantle in vivo. However, direct comparisons between current day MRI estimates and the quantitative measurements of early anatomists have been limited. Here, we report on a simple, but nevertheless important cross‐analysis between the histological reports of von Economo and Koskinas on variation in thickness of the cortical mantle and MRI derived measurements of cortical thickness. We translated the von Economo cortical atlas to a subdivision of the commonly used Desikan–Killiany atlas (as part of the FreeSurfer Software package and a commonly used parcellation atlas in studies examining MRI cortical thickness). Next, values of “width of the cortical mantle” as provided by the measurements of von Economo and Koskinas were correlated to cortical thickness measurements derived from high‐resolution anatomical MRI T1 data of 200+ subjects of the Human Connectome Project (HCP). Cross‐correlation revealed a significant association between group‐averaged MRI measurements of cortical thickness and histological recordings (r = 0.54, P < 0.001). Further validating such a correlation, we manually segmented the von Economo parcellation atlas on the standardized Colin27 brain dataset and applied the obtained three‐dimensional von Economo segmentation atlas to the T1 data of each of the HCP subjects. Highly consistent with our findings for the mapping to the Desikan–Killiany regions, cross‐correlation between in vivo MRI cortical thickness and von Economo histology‐derived values of cortical mantle width revealed a strong positive association (r = 0.62, P < 0.001). Linking today's state‐of‐the‐art T1‐weighted imaging to early histological examinations our findings indicate that MRI technology is a valid method for in vivo assessment of thickness of human cortex. Hum Brain Mapp 36:3038–3046, 2015. © 2015 Wiley Periodicals, Inc.
Age and sex influence on bone and blood lead concentrations in a cohort of the general population living in Toronto

Objective: To study the age and sex influence on bone and blood lead concentrations in a cohort of the general population living in Toronto. Approach: A 109Cd K x-ray fluorescence (KXRF) measurement system was used from 2009 to 2011 in a study that measured the bone lead (Pb) concentration of 263 environmentally exposed individuals residing in Toronto, Ontario, Canada. Tibia (cortical bone) and calcaneus (trabecular bone) lead contents were measured in 134 males and 129 females between 1 and 82 years of age. Whole blood Pb concentration was measured by TIMS (thermal ionization mass spectrometer). Tibia (Ti) and calcaneus (Cal) Pb were examined versus the age of participants, taking into account uncertainties in bone Pb measurement values. Main results: No significant sex differences were observed in any of the age categories. Participants older than 50 years of age demonstrated the highest concentrations of Pb in their blood, tibia, and calcaneus bones. Significance: In most of the previous publications, uncertainty was not considered in the regression model of bone Pb and age. However, in this paper, we adjusted the bone Pb values for the uncertainty level. This had a significant influence in regression models of bone Pb and thus we recommend that uncertainty be considered in future studies.
Identification of mouse liver proteins on two‐dimensional electrophoresis gels by matrix‐assisted laser desorption/ionization mass spectrometry of in situ enzymatic digests

A number of proteins from a silver‐stained two‐dimensional (2‐D) electrophoresis gel of mouse liver whole‐cell lysate were identified by peptide mass mapping and sequene database searching. The excised protein spots were processed by in situ reduction and alkylation, followed by Lys‐C digestion. The masses of the resulting peptide mixtures were measured with a matrix‐assisted laser desorption/ionization (MALDI) reflectron‐time‐of‐flight mass spectrometer. These masses were used successfully to search a protein sequence database. Optimized silver staining and digestion protocols allowed proteins to be identified routinely at the low picomole level. The high mass accuracy and resolution provided by delayed extraction were important for high specificity in the database search. Fragment ion data obtained by MALDI post‐source decay (PSD) measurements not only provided confirmation of peptide identification, but could be used to identify the protein from a single peptide without spectral interpretation.
Development of Control System for Inverted Wheeled Robot on a Ship: Predicting Ship's Rolling Motion

This paper proposes a predictive control system for balancing an inverted wheeled robot on a ship using both the autoregressive model and a Kalman filter. In general, the control system of inverted wheeled robots is designed on the assumption that the ground does not move. However, a ship has six degrees of freedom. Therefore, a method of predicting the ship's motion was required in order to control the balancing inverted wheeled robot on the ship. This study was focused on the ship's rolling motion. On the ship, the rolling motion was predicted by the autoregressive model and a Kalman filter. Then, the inverted wheeled robot was controlled by adding accelerations to the inverted wheeled robot for canceling out the inertia forces of the predicted rolling motion. The effectiveness of the proposed control system was indicated with experimental results.
Compressed spectral arrays of patients with fulminant hepatic failure in hepatic coma undergoing liver transplantation

Assessing the coma status of patients with fulminant hepatic failure (FHF) is important for determining the reversibility of brain damage and for properly timing liver transplantation. The compressed spectral array (CSA) method is a frequency analysis technique that processes electroencephalogram signals by computer to facilitate on‐line interpretation. This method has been used to monitor the consciousness levels of neurointensive care unit patients. In this study, we determined whether CSA could be used to assess the coma status of patients with FHF, and whether CSA provided information that was useful in deciding when to proceed with liver transplantation. CSA recording was carried out in 17 FHF patients with encephalopathy (coma grade III–IV) who underwent living‐related liver transplantation between August 1997 and May 1999. Recording was performed with a Neuromonitor OEE‐72044 (NIHON KOHDEN, Osaka, Japan) every 24 h before and after transplantation, until the patients regained consciousness. The CSAs of healthy controls were distributed almost equally between 0 and 16 Hz. The CSAs of FHF patients in hepatic coma were classified into three patterns. Eight of the 17 patients showed very prominent slow waves of about 2 Hz (group A), and seven patients showed strongly suppressed rapid waves between 8 and 16 Hz (group B). The remaining two patients showed CSA patterns that were similar to those of healthy controls, even though these patients were comatose (group C). Abnormal CSA patterns were observed in 15 of the 17 patients (88%). Group B patients seemed to have higher coma grades than did group A patients. Sixteen patients underwent liver transplantation, completely recovered from hepatic encephalopathy, and subsequently showed CSA patterns similar to those of healthy controls. One patient died without regaining consciousness. These results suggest that CSA is useful in assessing the coma status of FHF patients and in evaluating electrophysiological recovery from hepatic coma after liver transplantation.
Tat-mediated Intracellular Delivery of T-bet Protein into THP-1 Cells can Induce Th1-Type Response

T-bet, a Th1-specific transcription factor, can promote the production of IFN-γ. IFN-γ is the principal Th1 effector cytokine and it has a crucial role in Th1 differentiation, which can drive the differentiation of naïve CD4+T cells into T-helper 1 (Th1) cells. In our study, a human T-bet gene was fused with a gene fragment encoding HIV-1 protein transduction domain in a bacterial expression vector to produce a Tat/T-bet fusion protein. The expressed and purified Tat/T-bet proteins were transduced efficiently into THP-1 cells in a time- and dose-dependent manner; when Tat/T-bet pretreated THP-1 cells were co-cultured with CD4+T cells, the IFN-γ level increased higher to about 7 pg/ml, 10-folds as compared with the normal level when tested at 48 hours. The results demonstrated that the Tat/T-bet fusion protein can be efficiently transduced into antigen-presenting cells (APCs) like THP-1 cells and then regulated Th1/Th2 balance, which may act as a potential tool for gene therapy.
Coverage and quality of oral cancer information in the popular press: 1987-98.

OBJECTIVES National data show a lack of knowledge and misinformation about oral cancer and its early detection among the general public. A major source of health information is the popular press. For that reason this study reviewed coverage and quality of news items on the topic of oral cancer in the popular press. In addition, the number and types of tobacco advertisements in women and men's magazines were recorded for a one-year period. METHODS Articles from magazines and newspapers were retrieved from the Magazine Index (1987 to April 1998), Newspaper Abstract (1989 to April 1998) and the Health & Wellness (1987 to April 1998) databases. The articles were analyzed both for adequacy of content and information. RESULTS A total of 50 articles and news items including oral cancer were identified and analyzed, 18 from newspapers and 32 from magazines. Ninety-four percent of the articles mentioned at least one risk factor for oral cancer. More than half of the articles (56%) identified spit tobacco (chewing tobacco or snuff) as the major risk factor for oral cancer, while far fewer mentioned either cigarettes (32%) or cigars (12%). Over 50 percent of the articles did not mention warning signs for oral cancers. Fourteen percent suggested clinical oral cancer examinations by a health professional; only 8 percent advised the use of self-examination. A total of 417 tobacco advertisements (482 pages) were found among 22 magazines for the one-year period. They included 410 cigarette ads, seven cigar ads, and no spit tobacco ads. CONCLUSIONS This study demonstrates the lack of coverage about oral cancer in the popular press in the past decade and provides a partial explanation of the public's lack of knowledge and misinformation about oral cancers.