jimnoneill/paper-to-field-training huggingface dataset:
Genetic polymorphisms of serotonergic and dopaminergic neurotransmission differentially affect neurofunctional subsystems of working memory

Field: Neuroscience (Life Sciences)

In schizophrenia but also in other psychiatric disorders, e.g. in bipolar affective disorder and in attention-deficit/hyperactivity disorder, working memory impairments are considered to be core deficits and potential endophenotypic markers. Important to note, working memory is not a unitary system but comprises a set of different neurofunctional systems. Neuropharmacological studies suggest that these neurofunctional systems may be differentially modulated by serotonergic and dopaminergic neurotransmission. In the present study, we investigated the influence of genetic polymorphisms with direct impact on either the serotonergic or the dopaminergic system on the functional capacities of brain systems underlying verbal and visuospatial working memory. Consistent with our hypothesis, the DAT1 polymorphism had a significant and selective effect on visuospatial working memory capacity whereas presence of the “short“ allele of the 5HTT polymorphism significantly (and selectively) affected verbal working memory capacity. These findings provide evidence that genetic polymorphisms of serotonergic and dopaminergic neurotransmission differentially affect neurofunctional subsystems of working memory, and this may have implications for further systematic study of the pathophysiology of psychoses and for the development of individualized therapies.
A phase I/II study of nintedanib and capecitabine in refractory metastatic colorectal cancer.

Field: Medicine (Health Sciences)

759 Background: Refractory metastatic colorectal cancer patients (mCRC) have a poor prognosis with median survival of 4-6 months. Nintedanib is a TKI which inhibits VEGFR, PDGFR, and FGFR with preclinical efficacy in bevacizumab resistant CRC. This phase I/II study sought to evaluate the recommended phase II dose (RP2D) and efficacy of nintedanib and capecitabine in refractory mCRC patients. Methods: Key eligibility criteria included histologically proven mCRC, ECOG PS of 0 or 1, progression/intolerance to a fluoropyrimidine, oxaliplatin, irinotecan, and anti-EGFR therapy for RAS wt patients. Prior regorafenib, uncontrolled hypertension ( ≥ 160/90), recent clinically significant thrombosis/hemorrhage, or prior intolerance to capecitabine were exclusionary. Doses were escalated across 2 planned dose levels (DL) in a standard 3+3 design, with escalating doses of capecitabine. DLT observation window was the first 3 weeks after dosing. The primary endpoint was establishment of the RP2D. Results: 10 patients were enrolled across 2 dose levels. 1 patient withdrew consent and was replaced. 5 (50%) were PS 0. No grade 4 or 5 AEs were observed. No DLTs were observed. 2/10 (20%) of patients experienced a grade 3 AE, including hyperbilirubinemia (10%), AST elevation (10%), diarrhea (10%), dehydration (10%), and weakness (10%). The most common treatment-related AEs included palmar-plantar eythrodysesthesia (PPE) (50%), diarrhea (40%), stomatitis (30%), nausea (20%), vomiting (20%), and fatigue (20%). The RP2D was determined to be capecitabine 1000 mg/m2 divided bid and nintedanib 200 mg bid. PK data will be presented. Conclusions: Treatment was well tolerated. Most of the observed AEs were grade 1 or 2, without a marked difference between DLs. PPE was readily managed with dose adjustments. The phase II study is ongoing at the RP2D. This study was approved and funded by the National Comprehensive Cancer Network (NCCN) Oncology Research Program from general research support provided by Boehringer Ingelheim Pharmaceuticals, Inc. Clinical trial information: NCT02393755.
The microtubule networks in lung epithelia are severed during Klebsiella pneumoniae infections

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

Klebsiella pneumoniae is an enteric bacterium known to cause pneumonia, urinary tract infections and pyogenic liver abscesses. Of these infections, patients who develop pneumonia have poor survival rates and alarming mortality rates of up to 44% in highly infected individuals. Many studies have focused on identifying bacterial components crucial to the disease process, but the underlying sub‐cellular mechanisms for disease progression have remained elusive. To begin to study these mechanisms, we assessed the cytoskeletal integrity of infected A549 lung epithelial cells and lung epithelia from infected C57Bl/6J mice. We found that the microtubule networks of the entire epithelia were either severed or fully disassembled even when there were no bacteria directly attached on the host cells. Since bacterial attachment was not necessary to cause microtubule disassembly, we hypothesized that a novel K. pneumoniae protein activates signalling cascades that target microtubule‐severing activity within these lung cells. To test this hypothesis, we first infected A549 cells with K. pneumoniae mutants deficient for known bacterially generated pathogenic proteins and found that none of those proteins triggered microtubule severing. Then, we created a genomic library of the entire K. pneumoniae genome. Out of the ~3000 known K. pneumoniae genes, we found that K. pneumoniae ytfL ( KP ytfL ) consistently triggered microtubule severing in infected A549 cells. Bioinformatic analysis showed that the C‐terminal domain of KP YtfL has a catalytic region that could activate host signalling cascades. We then sought to identify the host microtubule‐severing enzyme responsible for the epithelial cell phenotype. Through immunolocalization studies, we discovered that the katanin catalytic subunit A1 like 1 protein (KATNAL1) and the katanin regulatory subunit B1 protein (KATNB1) were at the precise sites of microtubule severing. To determine if KATNAL1 and KATNB1 were responsible for K. pneumoniae ‐induced severing, we deleted the gene for either KATNAL1 or KATNB1 in A549 cells using CRISPR. We then infected the cells and when all the infected wild type cells had disassembled microtubules, KATNAL1 and KATNB1‐deficient cells retained intact microtubules. Thus, KATNAL1 and KATNB1 contribute to the microtubule severing activity during K. pneumoniae infections. Taken together, our data indicates that KP YtfL is a novel protein effector that triggers the activation of KATNAL1 and KATNB1 to sever microtubules in infected lung epithelial cells. Through our study, we identified a novel bacterial mechanism to destabilize the microtubule networks of an entire epithelium through the activation of host cell microtubule severing enzymes. Support or Funding Information This study was funded by NSERC, Taiwan NHRI and SFU institutional funds. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
Parasite virulence and host resistance in a slave-making ant community

Field: Agricultural and Biological Sciences (Life Sciences)

Questions: Does virulence of socially parasitic slave-making ants vary in interactions with different host species? If so, can this be linked to host properties such as nest availability or resistance of host species? Study system: Our study system included three slave-making ant species, Polyergus breviceps, Formica puberula, and F. gynocrates, and two host species, F. occulta and F. sp. cf. argentea. Methods: We measured slave-maker virulence by comparing the mortality rates of host nests that were raided by slave-makers to host nests that were not raided. To determine whether slave-makers that were more likely to over-exploit slave resources were more prudent (lower virulence), we compared the percentage of nests that were raided for each host species. To determine whether variation in slave-maker virulence was due to different levels of host resistance, we compared the aggressiveness of the two host species towards slave-makers during slave raids, reasoning that nests of a more aggressive host species would show higher survivorship. Results: Slave-makers were highly virulent in association with the host, F. sp. cf. argentea, but more benign in interactions with F. occulta. Formica occulta was not universally more aggressive against slave-makers than F. sp. cf. argentea, suggesting that this alone is not a sufficient explanation for the higher survivorship of this species. Slave-makers that specialized on F. occulta were at higher risk of over-exploiting resources, indicating that more prudent slave-maker strategies might be selected for in interactions with this host.
Autophosphorylation-Dependent Activation of a Calcium-Dependent Protein Kinase from Groundnut1

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

Abstract Ca2+-dependent protein kinases (CDPKs) containing a calmodulin-like domain integrated in their primary sequence are present primarily in plants. A member of this family was characterized from the groundnut (Arachis hypogea) plant and called GnCDPK (M. DasGupta [1994] Plant Physiol 104: 961–969). GnCDPK specifically uses the myosin light chain synthetic peptide (MLCpep), which is the phosphate-accepting domain of smooth muscle myosin light chains (KKRPQRATSNVFS), as an exogenous substrate under in vitro experimental conditions. In this report we show that GnCDPK undergoes intramolecular autophosphorylation. This self-phosphorylation occurs in threonine residues in a Ca2+-dependent (K0.5 = 0.5 μm) and calmodulin-independent manner. The kinase activity toward MLCpep and its sensitivity to Ca2+ were unaffected by prior autophosphorylation when measured under saturating ATP concentrations. The role of autophosphorylation in the exogenous substrate MLCpep phosphorylation reaction was reinvestigated at low ATP concentrations. A pronounced lag time of 1 to 2 min, followed by a linear increase of activity for 7.5 min, was seen in the initial rate of MLCpep phosphorylation under such suboptimal conditions. Prior autophosphorylation completely abolished this lag phase, and a sharp rise of exogenous substrate phosphorylation was seen from the 1st min. Our results suggest that autophosphorylation is a prerequisite for the activation of GnCDPK.
Highly Reversible Ambipolar Photocurrents by Modulating Ta in Ba2Bi2–xTaxO6 Double Perovskites

Field: Materials Science (Physical Sciences)

Ta5+-doped Ba2Bi2–xTaxO6 (0.2 ≤ x ≤ 0.8) double perovskites are synthesized by a soft chemical sol–gel method. X-ray diffraction (XRD) results show the formation of a double perovskite structure. Systematic shifts of Bragg diffraction peaks to larger angles confirm the incorporation of increasing amounts of Ta5+ dopant ions in the Ba2Bi2O6 (BBO) crystal lattice. The optical absorption spectra and Tauc plots reveal a monotonic increase of the optical band gaps for Ba2Bi2–xTaxO6 (0.2 ≤ x ≤ 0.8) from 1.5 to 2.3 eV. Photoelectrochemical (PEC) and electrochemical tests signify the advantages of doping Ta5+ in improving the photoelectrode resistance to electrochemical corrosion. Highly reversible ambipolar photocurrents are observed for photoelectrodes with x ≥ 0.4 that can be further enhanced by anodic or cathodic poling treatment for facilitated interface photocharge injection. Ba2Bi1.6Ta0.4O6 photoelectrodes exhibit both the highest cathodic photocurrent of 65.5 μA cm–2 at 0 VRHE with an onset potential of 1.43 VRHE, and the highest anodic photocurrent of 37 μA cm–2 at 2 VRHE with an onset potential of 1.03 VRHE among other Ta5+ containing counterpart samples. The deteriorating PEC photocurrents of photoelectrodes with x ≥ 0.5 are the result of both inferior light absorption ability due to large band gaps and lower charge carrier concentrations due to defect compensation. The understanding and control of this switchable-photocurrent phenomenon by doping strategies are significant to further tailor the electronic band structure for compatible homojunctions of BBO-based double perovskites.
The time course of chromatic and achromatic information extraction in a face-gender discrimination task

Field: Psychology (Social Sciences)

A previous study using the Bubbles technique (Dupuis-Roy, et al., 2009) showed that the eyes, the eyebrows, and the mouth were the most potent features for face-gender discrimination (see also Brown & Perrett, 1993; Russell, 2003, 2005). Intriguingly, the results also revealed a large positive correlation between the mouth region and rapid correct answers. Given the highly discriminative color information in this region, we hypothesized that the extraction of color and luminance cues may have different time courses. Here, we tested this possibility by sampling the chromatic and achromatic face cues independently with spatial and temporal Bubbles (see Gosselin & Schyns, 2001; Blais et al., 2009). Ninety participants (45 men) completed 900 trials of a face-gender discrimination task with briefly presented sampled faces (200 ms). To create a stimulus, we first isolated the S and V channels of the HSV color space for 300 color pictures of frontal-view faces (average interpupil distance of 1.03 deg of visual angle) and adjusted the S channel so that every color was isoluminant (±5 cd/m[sup]2[/sup]); then, we sampled S and V channels independently through space and time with 3D Gaussian windows. The group classification image computed on the response accuracy revealed that in the first 60 ms, participants used the color in the right eye-eyebrow and mouth regions, and that they mostly relied on the luminance information located in the eyes-eyebrows regions later on (>60 ms). Further classification images were computed for each gender-stimulus category. The results indicate that chromatic information in the mouth region led to systematic categorization errors. An analysis of the chromatic information available in this facial area suggests that this is not due to our face database, but rather represents a perceptual bias. Altogether, these results help to disentangle the relative contributions of chromatic and luminance information in face-gender discrimination. Meeting abstract presented at VSS 2013
Simulation of the effects of hypothetical residential development on water levels in Graber Pond, Middleton, Wisconsin

Field: Environmental Science (Physical Sciences)

An investigation of the effects of hypothetical residential development in the Graber Pond watershed was done by the U.S. Geological Survey in cooperation with the city of Middleton. The investigation entailed evaluation of the existing (1989) water budget and water-level conditions for the pond and the water-level conditions expected to result from the hypothetical development that may occur by the year 2000. A water-budget model was calibrated to closely match water levels observed from July 18-August 31, 1989. Water input to the pond during this period was computed to be about 2.58 feet. Of this, about 25 percent (0.65 foot) was from direct rainfall on the pond surface, about 19 percent (0.50 foot) was from storm runoff, and about 55 percent (1.43 feet) was discharge from a nearby manufacturing plant. Simulation of the hypothetical development conditions in the watershed predicts that the average late-summer pond level may rise about 0.7 foot.
Weighted Moving Average Passive Aggressive Algorithm for Online Portfolio Selection

Field: Computer Science (Physical Sciences)

Passive aggressive algorithms for online portfolio selection, such as PAMR, were recently shown empirically to achieve state-of-the-art performance in various stock markets. Inspired by the multi-period mean reversion principle in Antic or Algorithm, we present a passive aggressive algorithm by introducing a moving averaged loss function and achieve a novel online portfolio selection strategy named "Weighted Moving Average Mean Reversion" (WMAMR). The strategy is able to effectively exploit the power of mean reversion for online portfolio selection. Extensive experiments on various real markets demonstrate the effectiveness of our strategy in comparison with PAMR, especially with transaction cost.
Form and function of the musteloids

Field: Agricultural and Biological Sciences (Life Sciences)

The musteloids are the most speciose of the carnivorans and have a global distribution. They display a wide diversity of morphological and physiological form and function, which have been shaped by their adaptation to a wide variety of ecological niches, ranging from the Arctic to the tropics and deserts to the seas. This chapter explores how several morphological and physiological adaptations are key to their successful diversification, including an elongated body, a highly insulating pelage, powerful teeth and jaws, anal sacs for olfactory communication or chemical defence, and reproductive physiologies that allow females to optimise their reproductive output. While many of these adaptations are shared by other carnivorans, it is their combination in musteloids that has allowed them to diversify so successfully globally.
Diagnosing latent tuberculosis in immunocompromised patients measuring blood IP-10 production capacity: An analysis of chronic renal faulire patients

Field: Medicine (Health Sciences)

Objective: Patients undergoing haemodialysis for chronic renal failure (CRF-HD) are at risk of latent tuberculosis infection (LTBI). The effectiveness of using blood IP-10 production capacity to diagnose LTBI in CRF-HD patients was analysed. Patients and Method: The study enrolled 50 CRF-HD patients. Interferon-gamma release assay (IGRA) was done using Quantiferon G-In-Tube (QFG-IT) system. Blood IP-10 production capacity was measured using the QFG-IT system tubes. Tuberculin skin testing (TST) was performed on the same day and the test results were compared. Results: TST turned out to be positive in 36.4% of the patients and QFG-IT in 54% of them. After stimulation with specific tuberculosis antigens, blood IP-10 levels increased noticeably. The antigen-stimulated blood IP-10 level was significantly higher in patients who were either TST or QFG-IT positive than in patients whose tests were negative (p=0.0001). Using 4.02 pg/mL as the threshold for stimulated blood log-transformed IP-10 level, good agreement was observed between IP-10 and QFG-IT results (κ=1). Conclusion: Blood IP-10 level, which can be measured simply, provides results equivalent to interferon-γ release assays for the diagnosis of LTBI in CRF-HD patients.
Energy and Mineral Resources Exploitation in the Delignitization Era: The Case of Greek Peripheries

Field: Economics, Econometrics and Finance (Social Sciences)

The efficient and sustainable exploitation of energy resources may secure a sustainable economic growth for different regions. However, the peripheries are subject to social, economic, and political constraints, with limited power over energy management. The present work examines regional convergence in exploitation efficiency as synopsized in the GDP generated by energy and minerals in an era of the country’s efforts to shut down the lignite-run power production. With the assistance of panel unit root tests, we confirm non convergence of the variables employed, an expected result given the fact that different energy sources are being used for energy production by each different periphery, generating different economic results. In the second stage the methodology employed is a Bayesian vector auto-regressive model (BVAR) with an informative prior on the steady state. The particular methodology outperforms the conventional VAR methodology due to limited degrees of freedom. The Impulse response analysis and the Variance Decomposition analysis confirmed interlinkages among the regions studied. This result implies that the growth generated by different energy and mineral resources are interconnected. Furthermore, the energy transition taking place in Megalopoli and West Macedonia, where the two greatest lignite industries were located until recently, affects the growth generated by energy and resource exploitation for all the other peripheries, according to our findings. The novelty of the present work stands on the concept to detect interlinkages of energy and resources-based growth for the peripheries in Greece with the assistance of the Bayesian Var. The results of the present work are significant, since our findings suggest to policy makers tools to promote economic growth generated by energy based on alternative energy sources, including the environmentally friendly ones, by taking into consideration the interlinkages established by the existing infrastructure and the conventional energy sources used.
Environmental Triazole Induces Cross-Resistance to Clinical Drugs and Affects Morphophysiology and Virulence of Cryptococcus gattii and C. neoformans

Field: Immunology and Microbiology (Life Sciences)

ABSTRACT Cryptococcus gattii and Cryptococcus neoformans are environmental fungi that cause cryptococcosis, which is usually treated with amphotericin B and fluconazole. However, therapeutic failure is increasing because of the emergence of resistant strains. Because these species are constantly isolated from vegetal materials and the usage of agrochemicals is growing, we postulate that pesticides could be responsible for the altered susceptibility of these fungi to clinical drugs. Therefore, we evaluated the influence of the pesticide tebuconazole on the susceptibility to clinical drugs, morphophysiology, and virulence of C. gattii and C. neoformans strains. The results showed that tebuconazole exposure caused in vitro cross-resistance (CR) between the agrochemical and clinical azoles (fluconazole, itraconazole, and ravuconazole) but not with amphotericin B. In some strains, CR was observed even after the exposure ceased. Further, tebuconazole exposure changed the morphology, including formation of pseudohyphae in C. neoformans H99, and the surface charge of the cells. Although the virulence of both species previously exposed to tebuconazole was decreased in mice, the tebuconazole-exposed colonies recovered from the lungs were more resistant to azole drugs than the nonexposed cells. This in vivo CR was confirmed when fluconazole was not able to reduce the fungal burden in the lungs of mice. The tolerance to azoles could be due to increased expression of the ERG11 gene in both species and of efflux pump genes ( AFR1 and MDR1 ) in C. neoformans . Our study data support the idea that agrochemical usage can significantly affect human pathogens present in the environment by affecting their resistance to clinical drugs.
P5418Predictors of pulmonary artery hypertension recovery after Trans Aortic Valve Implantation

Field: Medicine (Health Sciences)

Pulmonary hypertension, congenital and acquired 1149are not at risk for the development of PH.However, patients with high pulmonary pressures require close follow-up, since PH persists in a substantial part of patients.Especially patients with high NYHA functional class and impaired RV function at baseline are at risk.
Habitat use and activities of the piping plover, Charadrius melodus, wintering on South Padre Island, Texas

Field: Agricultural and Biological Sciences (Life Sciences)

The Piping Plover, Charadrius melodus, is endangered in its breeding sites and threatened in its wintering sites. This migratory shorebird spends 3 to 4 months on northern U.S. and southern Canadian breeding sites and the remainder of the year in Gulf of Mexico, Caribbean, and southern U.S. wintering sites. Up to 2.4% of the estimated Piping Plover population remains for the 9 to 10 month non-breeding season on South Padre Island (S.P.I.). During the non-breeding season, I conducted censuses at 15 sites in the southern portion of South Padre Island to determine Piping Plover habitat preferences. Piping Plovers prefer bay side flats as opposed to beach areas on South Padre Island, and habitat use is determined by conditions such as exposure and wetness of bay side habitats. Piping Plovers tend to forage in habitats close to the Laguna Madre, such as mud flats and roost farther away on the sand flats.