Miracle-dz/UniFAR-FTUs huggingface dataset:
PACAP stimulates insulin secretion but inhibits insulin sensitivity in mice.

Although pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates insulin secretion, its net influence on glucose homeostasis in vivo has not been established. We therefore examined the action of PACAP-27 and PACAP-38 on insulin secretion, insulin sensitivity, and glucose disposal as derived from the minimal model of glucose disappearance during an intravenous glucose tolerance test in anesthetized mice. PACAP-27 and PACAP-38 markedly and equipotently potentiated glucose-stimulated insulin secretion, with a half-maximal effect at 33 pmol/kg. After PACAP-27 or PACAP-38 (1.3 nmol/kg), the acute (1-5 min) insulin response was 3.8 ± 0.4 nmol/l (PACAP-27) and 3.3 ± 0.3 nmol/l (PACAP-38), respectively, vs. 1.4 ± 0.1 nmol/l after glucose alone ( P < 0.001), and the total area under the curve for insulin (AUCinsulin) was potentiated by 60% ( P < 0.001). In contrast, PACAP-27 and PACAP-38 reduced the insulin sensitivity index (SI) [0.23 ± 0.04 10-4min-1/(pmol/l) for PACAP-27 and 0.29 ± 0.06 10-4min-1/(pmol/l) for PACAP-38 vs. 0.46 ± 0.02 10-4min-1/(pmol/l) for controls ( P < 0.01)]. Furthermore, PACAP-27 or PACAP-38 did not affect glucose elimination determined as glucose half-time or the glucose elimination rate after glucose injection or the area under the curve for glucose. Moreover, glucose effectiveness and the global disposition index (AUCinsulin times SI) were not affected by PACAP-27 or PACAP-38. Finally, when given together with glucose, PACAP-27 did not alter plasma glucagon or norepinephrine levels but significantly increased plasma epinephrine levels. We conclude that PACAP, besides its marked stimulation of insulin secretion, also inhibits insulin sensitivity in mice, the latter possibly explained by increased epinephrine. This complex action explains why the peptide does not enhance glucose disposal.
Thinking about computational thinking

Jeannette Wing's call for teaching Computational Thinking (CT) as a formative skill on par with reading, writing, and arithmetic places computer science in the category of basic knowledge. Just as proficiency in basic language arts helps us to effectively communicate and in basic math helps us to successfully quantitate, proficiency in computational thinking helps us to systematically and efficiently process information and tasks. But while teaching everyone to think computationally is a noble goal, there are pedagogical challenges. Perhaps the most confounding issue is the role of programming, and whether we can separate it from teaching basic computer science. How much programming, if any, should be required for CT proficiency? We believe that to successfully broaden participation in computer science, efforts must be made to lay the foundations of CT long before students experience their first programming language. We posit that programming is to Computer Science what proof construction is to mathematics, and what literary analysis is to English. Hence by analogy, programming should be the entrance into higher CS, and not the student's first encounter in CS. We argue that in the absence of programming, teaching CT should focus on establishing vocabularies and symbols that can be used to annotate and describe computation and abstraction, suggest information and execution, and provide notation around which mental models of processes can be built. Lastly, we conjecture that students with sustained exposure to CT in their formative education will be better prepared for programming and the CS curriculum, and, furthermore, that they might choose to major in CS not only for career opportunities, but also for its intellectual content.
Competing Interpretations of Disorder Codes in SNOMED CT and ICD

Under ontological scrutiny we have identified two competing interpretations of disorder concepts in SNOMED. Should codes be interpreted as representing pathological conditions themselves or the situations in which a patient has those conditions? This difference has significant implications for the proposed harmonization between SNOMED CT and the new ICD-11 disease classification and indeed for any systematic review of the correctness of the SNOMED CT hierarchies. Conditions themselves are distinct, whereas in any given situation a patient may have more than one condition. In such cases, SNOMED codes that represent combinations of conditions - which can be regarded as "additive" - are evidence for interpreting the codes as referring to situations. There are clearly some such codes. We conducted a survey to determine the extent of this phenomenon. Three criteria were used - analysis of the SNOMED CT fully specified name, the corresponding logical definition, and the children of the concept under scrutiny. All three showed that at least 11% of concepts met our criteria for representing situations rather than conditions, with a satisfactory inter-rater reliability for the first two. We, therefore, conclude that if a uniform interpretation of SNOMED disorder codes is desired, they should be interpreted as representing situations.
AXL-dependent infection of human fetal endothelial cells distinguishes Zika virus from other pathogenic flaviviruses

Significance Zika virus (ZIKV) causes microcephaly, whereas other related pathogenic flaviviruses do not. To reach the fetal brain, a virus must be transported from the maternal to the fetal circulation, which requires crossing of the placental barrier. Our studies demonstrate that mammalian cell-derived ZIKV, but not two other globally relevant flaviviruses, efficiently infects fetal endothelial cells, a key component of the placental barrier, because only ZIKV can efficiently use the cell-surface receptor AXL. These data suggest that use of AXL allows ZIKV to enter the fetal bloodstream to gain access to other fetal tissues. Thus, this study provides insight into the unique properties of ZIKV that contribute to its ability to cause microcephaly and other congenital infections and diseases. Although a causal relationship between Zika virus (ZIKV) and microcephaly has been established, it remains unclear why ZIKV, but not other pathogenic flaviviruses, causes congenital defects. Here we show that when viruses are produced in mammalian cells, ZIKV, but not the closely related dengue virus (DENV) or West Nile virus (WNV), can efficiently infect key placental barrier cells that directly contact the fetal bloodstream. We show that AXL, a receptor tyrosine kinase, is the primary ZIKV entry cofactor on human umbilical vein endothelial cells (HUVECs), and that ZIKV uses AXL with much greater efficiency than does DENV or WNV. Consistent with this observation, only ZIKV, but not WNV or DENV, bound the AXL ligand Gas6. In comparison, when DENV and WNV were produced in insect cells, they also infected HUVECs in an AXL-dependent manner. Our data suggest that ZIKV, when produced from mammalian cells, infects fetal endothelial cells much more efficiently than other pathogenic flaviviruses because it binds Gas6 more avidly, which in turn facilitates its interaction with AXL.
Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms.

Exogenous administration of glucagon-like peptide-1-(7-36) amide (GLP-1), an insulinotropic hormone, inhibits gastric emptying and acid secretion in humans. The role of GLP-1 as a regulator of gastric function is elusive. In gastric fistula rats, vagal afferent denervation and peripheral administration of the GLP-1 receptor antagonist exendin(9-39) amide enhanced emptying of a glucose meal, whereas intracerebroventricular exendin was ineffective. The rate of saline emptying was attenuated by peripheral as well as by central administration of GLP-1, and pretreatment with exendin by the respective routes reversed the inhibition by GLP-1. Vagal afferent denervation abolished the central and peripheral action of GLP-1 on gastric emptying. Neither peripheral cholinergic nor adrenergic blockade altered the delay of methyl cellulose meal emptying by intracisternal GLP-1 injection. Acid secretion in conscious pylorus-ligated rats was inhibited by intracisternal GLP-1 administration, whereas systemic GLP-1 was ineffective. These results support the notion that GLP-1 receptors participate in the central and peripheral regulation of gastric function. Furthermore, vagal afferent nerves mediate the inhibitory action of GLP-1 on gastric motor function. GLP-1 may be a candidate brain-gut peptide that acts as a physiological modulator of gastric function.
A method to account for the effect of hydrodynamics on polar organic compound uptake by passive samplers

Mass transfer coefficients of the water boundary layer (kw) were measured using alabaster dissolution kinetics in a diffusion cell that was operated at stirring rates between 90 min−1 and 600 min−1, aiming to provide a more robust characterization of the effect of hydrodynamics on the uptake of polar compounds by passive samplers, as compared with characterizations in terms of stirring rates and water flow velocities. The measured kw helped to quantitatively understand calcium sulfate transport through a poly(ethersulfone) membrane and 2 water boundary layers (at both sides of the membrane). Alabaster‐based kw value were used to understand atrazine transport in the diffusion cell, allowing the conclusion that atrazine transport in the membrane is via the pore space, rather than via the polymer matrix. The merits of measuring alabaster dissolution rates for passive sampler calibration and application in the field are discussed. The authors propose that passive sampler calibrations be carried out under controlled kw conditions, rather than under controlled stirring rates or flow velocities. This would facilitate the interpretation of passive sampler calibration studies and the translation of laboratory‐based water sampling rates to flow conditions that apply in the field. Environ Toxicol Chem 2017;36:1517–1524. © 2016 SETAC
VAGINAL DELIVERY OF A HYDROPHOBIC ANTIRETROVIRAL DRUG CSIC FOR HIV PREVENTION: NOVEL FORMULATION STRATEGIES FOR IMPROVED DRUG SOLUBILIZATION AND LYMPHATIC TARGETING

HIV epidemic is an ongoing health concern globally. Sexual transmission accounts for the overwhelming majority of new infections. Vaginal microbicides are under investigation as pre-exposure prophylaxis (PrEP) products for HIV prevention. Although progress has been made, the development of more efficacious products is warranted. Cervicovaginal tissue and draining lymph nodes contain an adequate amount of HIV target cells and play critical roles in HIV replication and sedimentation at the early stage of infection. Improved efficacy can be achieved with the use of specially designed drug delivery systems which achieve greater drug concentrations in these two sites of action. In this dissertation, we hypothesized that the hydrophobic microbicide candidate CSIC can be formulated in a polymeric vaginal film and a nanocrystal formulation with high loading capacities using multiple formulation strategies. We further hypothesized that the nano-delivery strategy can improve cervicovaginal tissue drug penetration and achieve lymphatic drug delivery. Series of preformulation studies were conducted to evaluate the physicochemical and biological properties of the drug candidate CSIC. The major challenge for CISC formulation development was identified as its hydrophobicity. Therefore, a cosolvent system comprising PEG 400, propylene glycol, and glycerin at a ratio of 5:2:1 has been optimized and utilized in a polymer based vaginal film formulation for increased drug solubility, long term stability, and lack of leakage. Additionally, a CSIC nanocrystal formulation, with a particle size of 243nm and near neutral surface charge, was developed. CSIC nanocrystals have been proved to possess increased drug saturation solubility, rapid mucus penetration properties, and improved drug permeation in the cervicovaginal tissue. More importantly, the pharmacokinetic study provided the first evidence of lymphatic targeting after intravaginal application without causing any epithelial damage. Furthermore, CSIC was able to release from the nanocrystals in a sustained mode, indicating its potential use as a coitally independent PrEP product that could improve user adherence. In summary, this work sets the stage to create new opportunities for sexually transmitted HIV prevention through the development of a novel dual targeting delivery system. The developed approaches can be used to deliver other drugs that lack solubility or require lymphatic targeting.
ClickBAIT-v2: Training an Object Detector in Real-Time

Modern deep convolutional neural networks (CNNs) for image classification and object detection are often trained offline on large static datasets. Some applications, however, will require training in real-time on live video streams with a human-in-the-loop. We refer to this class of problem as time-ordered online training (ToOT). These problems will require a consideration of not only the quantity of incoming training data, but the human effort required to annotate and use it. We demonstrate and evaluate a system tailored to training an object detector on a live video stream with minimal input from a human operator. We show that we can obtain bounding box annotation from weakly-supervised single-point clicks through interactive segmentation. Furthermore, by exploiting the time-ordered nature of the video stream through object tracking, we can increase the average training benefit of human interactions by 3-4 times.
User Experience Mining auf Basis von Online-Produktbewertungen

Die vorliegende Arbeit untersucht die Grenzen und Möglichkeiten einer automatischen Erfassung der User Experience (UX) von Produkten durch die Analyse von Online-Reviews. Hierzu wurde ein Tool entwickelt, das online verfügbare Produktbewertungen sammelt und mittels Methoden des Natural Language Processing sowie der Sentiment-Analyse aufbereitet, um die Ergebnisse auf die Werteskalen des User Experience Questionnaire (UEQ) abzubilden. Weiterhin präsentieren wir eine Evaluation des so erstellten Tools, indem wir die automatisch generierten Ergebnisse mit den Ergebnissen einer klassischen Benutzerstudie vergleichen. Es zeigt sich, dass automatisch erstellte UX-Analysen aus Online-Reviews zumindest eine grobe Annäherung zur UX eines Produkts zulassen – wenn auch nicht so differenziert wie ein von echten Anwendern vollständig ausgefüllter UEQ.
The interactions of lead (Pb) in lead free solder (Sn/Ag/Cu) system

The solder interaction of Pb within the Sn/Ag/Cu system was characterized using Differential Scanning Calorimetry (DSC). Components were then assembled with the Pb-free solder. Cross-sectioning and fine polishing were performed on the solder joints at the as-soldered stage and after temperature cycle readouts at 250, 500, 750, and 1000 cycles. The microstructure of the solder joints was examined using Scanning Electron Microscopy (SEM), and solder elements were mapped and identified by Energy-Dispersive X-ray (EDX) analysis. DSC detected Pb reaction with Sn/Ag at 179/spl deg/C and ternary compound formation. SEM/EDX found that Pb diffused into the Sn/Ag/Cu matrix during reflow soldering to form different microstructures, namely CuSn, SnAg, SnPbAg, and Pb-rich phases. The SnAg structure was found as a rod/needle morphology that was detrimental to solder joint reliability. During temperature cycling, this structure loosened its embedding effects due to grain-boundary sliding in the solder matrix, which accelerated solder fatigue crack propagation. Solutions to this problem are discussed.
Three-dimensional atrial wall thickness maps to inform catheter ablation procedures for atrial fibrillation.

AIMS Transmural lesion formation is critical to success in atrial fibrillation ablation and is dependent on left atrial wall thickness (LAWT). Pre- and peri-procedural planning may benefit from LAWT measurements. METHODS AND RESULTS To calculate the LAWT, the Laplace equation was solved over a finite element mesh of the left atrium derived from the segmented computed tomographic angiography (CTA) dataset. Local LAWT was then calculated from the length of field lines derived from the Laplace solution that spanned the wall from the endocardium or epicardium. The method was validated on an atrium phantom and retrospectively applied to 10 patients who underwent routine coronary CTA for standard clinical indications at our institute. The Laplace wall thickness algorithm was validated on the left atrium phantom. Wall thickness measurements had errors of <0.2 mm for thicknesses of 0.5-5.0 mm that are attributed to image resolution and segmentation artefacts. Left atrial wall thickness measurements were performed on 10 patients. Successful comprehensive LAWT maps were generated in all patients from the coronary CTA images. Mean LAWT measurements ranged from 0.6 to 1.0 mm and showed significant inter and intra patient variability. CONCLUSIONS Left atrial wall thickness can be measured robustly and efficiently across the whole left atrium using a solution of the Laplace equation over a finite element mesh of the left atrium. Further studies are indicated to determine whether the integration of LAWT maps into pre-existing 3D anatomical mapping systems may provide important anatomical information for guiding radiofrequency ablation.
Screening of Deoxynivalenol Producing Strains and Elucidation of Possible Toxigenic Molecular Mechanism

In this study, seven strains of Fusarium graminearum were isolated from wheat, of which six were identified to produce deoxynivalenol and the production of deoxynivalenol was assessed. F. graminearum strain Fg1 was noted to produce 1.0 μg/g deoxynivalenol during the incubation period in the Czapek yeast broth, while none was detected in F. graminearum strain Fg2. Hence, the differences in proteomes and transcriptomes of Fg1 and Fg2 were compared to analyze the mechanism underlying deoxynivalenol production. Among the 66 significantly differentially expressed proteins in Fg1, 39 and 27 were more or less abundant expressed. Functional analysis suggested that the enzymes involved in the methylerythritol 4-phosphate and mevalonate pathways, which provide a substrate for biosynthesis of farnesyl pyrophosphate, a precursor of DON, were activated in Fg1. The transcriptomics data demonstrated that the expression level of a majority of genes, including trichothecene biosynthetic genes, protein kinases, and transcription factors, involved in trichothecene biosynthesis was higher in Fg1 than in Fg2. The results also revealed differential expression profiles of deoxynivalenol biosynthesis genes in strains Fg1 and Fg2, which emphasized their deoxynivalenol producing ability and the underlying mechanism.
Restoration of transient outward current by norepinephrine in cultured canine cardiac myocytes.

The mechanism for the reduction of the transient outward K+ current ( I to) in diseased myocardium is unknown. To identify potential mechanisms, the reduction of I toand its subsequent restoration by norepinephrine (NE) were studied in cultured canine epicardial myocytes. After myocytes were cultured for 9 days ( day 9), I to density was decreased compared with density on the day of isolation ( day 0) (3.2 ± 0.4 vs. 10.4 ± 0.4 pA/pF; mean ± SE). The time constant of current decay (τdecay) was increased, the time course of recovery from inactivation was prolonged, and the half-inactivation voltage ( V 1/2) was shifted to less negative potentials. Exposure of myocytes on day 8 to 1 μM NE or isoproterenol (Iso) for 1 h had no acute effect on I to but restored I to density to 7.6 ± 1.2 or 9.7 ± 2.3 pA/pF, respectively, on day 9. Recovery from inactivation and τdecay remained slowed, and V 1/2 remained shifted to less negative potentials. The effects of NE and Iso were blocked by actinomycin D and were not mimicked by phenylephrine or phorbol ester. A-23187 (1 μM) also restored I to. Thus β-adrenergic agonists restored normal I to density, but not normal I tokinetics, in cultured epicardial myocytes, possibly via increased intracellular Ca2+ concentration.
A reduction in SK channels contributes to increased activity of hypothalamic magnocellular neurons during heart failure

Small conductance Ca2+‐activated K+ (SK) channels play an important role in regulating the excitability of magnocellular neurosecretory cells (MNCs). Although an increased SK channel function contributes to adaptive physiological responses, it remains unknown whether changes in SK channel function/expression contribute to exacerbated MNC activity under disease conditions. We show that the input–output function of MNCs in heart failure (HF) rats is enhanced. Moreover, the SK channel blocker apamin enhanced the input–output function in sham, although not in HF rats. We found that both the after‐hyperpolarizing potential magnitude and the underlying apamin‐sensitive IAHP are blunted in MNCs from HF rats. The magnitude of spike‐induced increases in intracellular Ca2+ levels was not affected in MNCs of HF rats. We found a diminished expression of SK2/SK3 channel subunit mRNA expression in the supraoptic nucleus of HF rats. Our studies suggest that a reduction in SK channel expression, but not changes in Ca2+‐mediated activation of SK channels, contributes to exacerbated MNC activity in HF rats.
Lung Cancer Risk after Exposure to Polycyclic Aromatic Hydrocarbons: A Review and Meta-Analysis

Typical polycyclic aromatic hydrocarbon mixtures are established lung carcinogens, but the quantitative exposure–response relationship is less clear. To clarify this relationship we conducted a review and meta-analysis of published reports of occupational epidemiologic studies. Thirty-nine cohorts were included. The average estimated unit relative risk (URR) at 100 μg/m3 years benzo[a]pyrene was 1.20 [95% confidence interval (CI), 1.11–1.29] and was not sensitive to particular studies or analytic methods. However, the URR varied by industry. The estimated means in coke ovens, gasworks, and aluminum production works were similar (1.15–1.17). Average URRs in other industries were higher but imprecisely estimated, with those for asphalt (17.5; CI, 4.21–72.78) and chimney sweeps (16.2; CI, 1.64–160.7) significantly higher than the three above. There was no statistically significant variation of URRs within industry or in relation to study design (including whether adjusted for smoking), or source of exposure information. Limited information on total dust exposure did not suggest that dust exposure was an important confounder or modified the effect. These results provide a more secure basis for risk assessment than was previously available.
The never-ending pas de deux Focus on "Capacitative Ca2+ entry is involved in cAMP synthesis in mouse parotid acini".

for what seems like eons, adenosine 3′,5′-cyclic monophosphate (cAMP) and Ca2+ have been competing for supremacy in cellular signaling. They still are. A study by Watson et al., the current article in focus (Ref. [8][1], see p. C557 in this issue), brings new insight to the sophisticated