Miracle-dz/UniFAR-FTUs huggingface dataset:
Ceramide Selectively Decreases Tau Levels in Differentiated PC12 Cells Through Modulation of Calpain I

Abstract: Ceramide has been recently proposed to be a signal mediator in several important physiological processes including apoptosis, cellular growth, and differentiation. Because the microtubule‐associated protein tau plays an important role in the establishment and maintenance of neuronal morphology, the effects of ceramide on tau were examined. Treatment of differentiated PC12 cells with the cell‐permeable ceramide derivative N‐acetylsphingosine (C2) resulted in a significant reduction in tau levels. Significant decreases in tau levels were also observed when the cells were treated with another ceramide derivative, N‐hexanoylsphingosine (C6). In addition, C2 treatment increased the levels of a calpain‐derived spectrin breakdown product but did not alter the levels of two cytoskeletal proteins, α‐actin and α‐tubulin. Because both tau and spectrin are proteolyzed in vitro by the calcium‐activated cysteine protease calpain, the effects of ceramide analogues on the activity of this protease were examined. Treatment of PC12 cells with C2 enhanced calcium‐stimulated proteolytic activity significantly, as revealed by monitoring the hydrolysis of the membrane‐permeable calpain‐selective fluorescence probe N‐succinyl‐l‐leucyl‐l‐leucyl‐l‐valyl‐l‐tyrosine‐7‐amido‐4‐methylcoumarin. This activity increase was not due to a direct effect of C2 on calpains, because C2 did not alter the activities of purified calpain I or II. In addition, C2 treatment of PC12 cells resulted in a significant increase in the levels of calpain I and, to a lesser extent, the levels of calpastatin (an endogenous calpain inhibitor protein), whereas the levels of calpain II were not changed. Moreover, treatment of the cells with the synthetic calpain‐specific inhibitor N‐carbobenzoxy‐l‐leucyl‐l‐leucyl‐l‐tyrosine diazomethyl ketone blocked the C2‐induced decreases in tau levels. These results indicate that tau levels are regulated in response to a physiological factor and, thus, have implications for ceramide‐mediated changes in normal and pathological neuronal processes.
Long Range Guided Wave Inspection Usage – Current Commercial Capabilities and Research Directions

Guided wave inspection of pipelines is now in routine use worldwide. The technique offers the possibility of rapid screening of long lengths of pipework for corrosion and other defects. A test range of 50m or more (25m in each direction) is commonly obtained from a single transducer position. Long range guided wave inspection techniques are also in development for several other applications, including the detection of corrosion in large areas of plates, the detection of cracking in railway lines, the detection of cracking in rockbolts, and the detection of corrosion in heat exchanger tubing.
Regulation of atmospheric CO 2 by deep-sea sediments in an Earth system model

[1] We have extended the GENIE-1 Earth system model to include a representation of sedimentary stratigraphy and the preservation of biogenic carbonates delivered to the ocean floor. This has enabled us to take a novel approach in diagnosing modern marine carbon cycling: assimilating observation of the calcium carbonate (CaCO3) content of deep-sea sediments with an ensemble Kalman filter. The resulting calibrated model predicts a mean surface sediment content (32.5 wt%) close to the observed value (34.8 wt%), and a global burial rate of CaCO3 in deep sea sediments of 0.121 PgC yr , in line with recent budget estimates of 0.10 0.14 PgC yr . We employ the GENIE-1 model in quantifying the multimillennial-scale fate of fossil fuel CO2 emitted to the atmosphere. In the absence of any interaction between ocean and sediments, an equilibrium partitioning of CO2 is reached within 1000 years of emissions ceasing, with 34% (645 ppm) remaining in the atmosphere out of a total fossil fuel burn of 4173 PgC. An additional 12% of CO2 emissions (223 ppm) are sequestered as bicarbonate ions (HCO3 ) by reaction with deep-sea carbonates (‘‘seafloor CaCO3 neutralization’’) on a timescale of 1.7 ka. Excess of carbonate weathering on land over deep-sea burial results in a further net transformation of 14% of CO2 emissions (261 ppm) into HCO3 (‘‘terrestrial CaCO3 neutralization’’) on a timescale of 8.3 ka. We have also assessed the importance of a changing climate in modulating the stabilization of atmospheric CO2 through ocean-sediment interaction. Increased ocean stratification suppresses particulate organic carbon export, which in turn enhances seafloor CaCO3 preservation. The resulting reduction in the sequestration of fossil fuel CO2 represents a new positive feedback on millennial-scale climate change. Citation: Ridgwell, A. , and J. C. Hargreaves (2007), Regulation of atmospheric CO2 by deep-sea sediments in an Earth system model, Global Biogeochem. Cycles, 21, GB2008, doi:10.1029/2006GB002764.
Top associated Higgs boson production channel ttH → 2 ` + 1 τ had at √ s = 13 TeV with the ATLAS experiment

The production of the Higgs boson in association with the top quarks allows a direct measurement of the Yukawa coupling as a key parameter of the Standard Model. A search for such process in multilepton final states mainly targeting the decays H→WW∗, ττ , and ZZ∗ is performed using 13.2 fb−1 of data recorded by the ATLAS detector in 2015 and 2016 at a center of mass energy √ s = 13 TeV. An overview of the final state with two same-charge light leptons (e or μ) and one hadronically-decaying τ is described in more detail. The best-fit value of the ratio of observed and Standard Model cross sections for the combined multilepton final states is 2.5 ± 0.7 (stat.) +1.1 −0.9 (syst.), which is consistent with the Standard Model expectation. 38th International Conference on High Energy Physics 3-10 August 2016 Chicago, USA ∗Speaker. †On behalf of the ATLAS Collaboration c © Copyright owned by the author(s) under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). http://pos.sissa. it/ P o S ( I C H E P 2 0 1 6 ) 1 1 3 7 Top associated Higgs production channel ttH→ 2`+1τhad in ATLAS Babar Ali
Nasopharyngeal Extranodal NK/T-Cell Lymphoma, Nasal Type: Retrospective Study of 18 Consecutive Cases in Guangzhou, China

Objective: The aim of this study was to investigate the frequency and clinicopathologic features of nasopharyngeal extranodal NK/T-cell lymphoma, nasal type (NKTCL), as well as DNA sequence variation of Epstein—Barr virus (EBV) in neoplastic cells harboring in NKTCLs from Guangzhou district. Materials and methods: The clinical data of 18 unselected consecutive nasopharyngeal NKTCLs in one institution were reviewed retrospectively. Immunohistochemical staining and EBV-encoded RNAs (EBERs) in situ hybridization were applied. DNA extraction, polymerase chain reaction (PCR), nested PCR, and sequencing for analyzing the C-terminal and N-terminal regions of LMP1 gene as well as BamHI F fragment of EBV were applied in 16 available samples. Results: NKTCLs accounted for 69.2% (18/26) of nasopharyngeal T- and NK-cell lineage non-Hodgkin lymphomas. In all, 10 out of 18 patients (55.56%) had cervical lymph node(s) involvement. The serum anti-EBV antibody level was elevated (VCA-IgA titer ≥1:40) in 6 of 12 available patients. Two major immunophenotypic subtypes, namely, TIA-1+/EBERs+/CD56+ (10 cases) and TIA-1+/EBERs+/CD56- (8 cases) could be recognized. Genotyping analysis revealed that 10 out of 13 cases (76.9%) of NKTCL were harbored with del-LMP1 [del-LMP1 (Gly335) variant 7 cases, del-LMP1 (Asp335) variant 3 cases]. XhoI-loss was shown in 8/11 cases (72.73%). BamHI “f” variant of Bam F fragment was shown only in 4/14 cases (28.57%). The most common combination was del-LMP1 (Gly335)/ XhoI-loss/F (6/9, 66.7%). Conclusions: The majority of nasopharyngeal T- and NK-cell lymphomas are NKTCL in Guangzhou district. The patients often have involvement of cervical lymph node(s) and an elevated level of serum anti-EBV antibodies. The CD56 expression rate seems lower than that found in sinonasal NKTCL. The most common EBV variant harboring in nasopharyngeal NKTCL seems somewhat different from that harboring in nasopharyngeal carcinoma in Guangzhou.
A New Approach to the Large-Eddy Simulation of High-Speed Compressible Flows

Abstract : All entirely new approach to the large-eddy simulation (LES) of high speed compressible turbulent flows is presented. In this new approach to large-eddy simulations, subgrid scale stress models go continuously to Reynolds stress models in the coarse mesh/infinite Reynolds number limit, where a Reynolds stress calculation (RANS) is done in parallel with the LES to get an estimate of the Kolmogorov length scale. Hence, this formally constitutes a combined LES/time dependent RANS capability. Here, the Reynolds stress model that is recovered in the coarse mesh limit has a dependence on rotational strains through strain-dependent coefficients as well as through anisotropic eddy viscosity terms which are usually neglected in subgrid scale models. Unlike in existing subgrid scale models, this new model has the correct dependence on the mesh size through the dimensionless ratio of the computational mesh size to the Kolmogorov length scale. It is this ratio that determines how well-resolved a computation is in the numerical simulation of turbulence and should be used to parameterize subgid scale models. Use is made of the Morkovin hypothesis in the formulation of compressible subgrid scale models. This allows for the description of supersonic turbulent flows provided that they are not in the hypersonic flow regime. A critical assessment of this new approach is provided along with a discussion of traditional approaches and the prospects for future applications to the high-speed compressible flows of technological importance.
p 38 MAPK is Activated by Vascular endothelial growth factor receptor 2 and is essential for shear stress-induced angiogenesis

Increased capillary shear stress induces angiogenesis in skeletal muscle, but the signaling mechanisms underlying this response are not known. We hypothesize that shear stress-dependent activation of vascular endothelial growth factor receptor 2 (VEGFR2) causes p38 and ERK1/2 phosphorylation, which contribute to shear stress-induced angiogenesis. Skeletal muscle microvascular endothelial cells were sheared (12 dynes/cm2, 0.5–24 hours). VEGFR2-Y1214 phosphorylation increased in response to elevated shear stress and VEGF stimulation. p38 and ERK1/2 phosphorylation increased at 2 hours of shear stress, but only p38 remained phosphorylated at 6 and 24 hours of shear stress. VEGFR2 inhibition abrogated p38, but not ERK1/2 phosphorylation. VEGF production was increased in response to shear stress at 6 hours, and this increased production was abolished by p38 inhibition. Male Sprague-Dawley rats were administered prazosin (50 mg/L drinking water, 1, 2, 4 or 7 days) to induce chronically elevated capillary shear stress in skeletal muscle. In some experiments, mini-osmotic pumps were used to dispense p38 inhibitor SB203580 or its inactive analog SB202474, to the extensor digitorum longus (EDL) of control and prazosin treated rats. Immunostaining and Western blotting showed increases in p38 phosphorylation in capillaries from rats treated with prazosin for 2 days but returned to basal levels at 4 and 7 days. p38 inhibition abolished the increase in capillary to muscle fibre ratio seen after 7 days of prazosin treatment. Our data suggest that p38 activation is necessary for shear stress-dependent angiogenesis.
Form and function of the glycocalyx on free cell surfaces.

Selected examples of the glycocalyx or cell coat on rickettsiae, bacteria, amoebae, sea-urchin eggs and the cat intestinal microvilli are illustrated and their functional roles are discussed. The differences in the form of various surface coats are noted; while many surface components are truely extraneous expend-able coatings, others are so firmly attached that they seem to be a permanent part of the cell. The fuzzy surface coat on the cat intestinal microvilli have been considered in some detail and some new observations on the form of the glycocalyx are presented. The enteric surface coat is not readily visualized in fractured surface replicas of glycerinated tissue but fixed cells frozen in distilled water when replicated after freeze-etching reveal a flamboyant array of a filamentous meshwork attached to the microvilli. This fuzzy coat layer is at least twice as thick in the freeze-etched preparations when compared to thin sectioned material. Fresh tissue frozen without fixation or glycerin treatment did not have a thick fuzzy coat. In its place a thin amorphous blanket-like layer was found.
Nishimura : Funding for financing economic growth – a Schumpeterian perspective

Having experienced prolonged stagnation after the global financial crisis of 2008, economists, market participants, and policymakers alike have arrived at the painful recognition that per capita real output has a long path toward recovering its pre-crisis level. To tackle this stagnation, the standard macroeconomic prescription is simple and straightforward: the policymaker should conduct an expansionary policy to fill the gap between actual and potential GDP, treating potential GDP as exogenously given. Although it is difficult to tell in real time whether the observed weakness in economic recovery is cyclical or structural, it seems obvious that the current GDP gap is large no matter how one measures the potential. Under this prescription, and facing the zero bound on nominal interest rates, central banks in advanced countries are currently employing unconventional measures, such as large-scale asset purchase programs.
VARIOUS ALTERNATIVES OF HYPOXIC TRAINING

Original scientific paper The aim of the paper was to compare the influence of three different alternatives of hypoxic training (a training in higher altitude – HA, an intermittent hypoxic training – IHT, and a hypoxic tent – HT). The research was executed on 10 athletes who all took part in higher altitude training and an intermittent hypoxic training. Four of the athletes from this sample took part in a training (a sleep) in a hypoxic tent. All the three alternatives lasted for approximately three weeks. In haematological indicators the number of erythrocytes, haemoglobin and hematocrit in HA and IHT increased from 3% to 4.9%. A more significant increase (25.3%, resp. 26.2%) was measured in reticulocytes. In HT we measured the increase of reticulocytes in 17.9%; however in the remaining indicators we observed even smaller increase, namely 0.7 – 2.3%. From the point of spiroergometric indicators we observed the most significant increase in the VO 2 max.kg-1 at ANT where we measured an increase of 8.7%, resp. 9.9%. Obviously, this indicator is directly influenced by the decrease of body weight, but also in absolute rate of VO 2 max at ANT we measured an increase (7%, resp. 7.7%), which indicates the increase of oxygen usability at ANT, thus the intensity corresponding to the competition load. In HT we also measured the increase in these parameters as well as a moderate decrease of body weight (0.3%), however only from 0.3 – 1.5%. From the point of effectiveness we confirmed a positive influence of hypoxic training in all the three methods (HA, IHT, HT), but according to our findings the influence of HA and IHT was significantly higher than in HT.
Kir Ülle Enrichment of gastrointestinal anaerobes by a novel technique

Author Title Number of Pages Date Kir Ülle Enrichment of gastrointestinal anaerobes by a novel technique 43 pages + 3 appendices 15.10. 2017 Degree Bachelor of Engineering Degree Programme Biotechnology and Chemical Engineering Specialization option Biotechnology and Food Engineering Instructors Teemu Rinttilä, Senior scientist Carola Fortelius, Head of Degree Programme This thesis was commissioned by a Finnish company Alimetrics Ltd., which specializes in life sciences. The aim was to isolate bacterial communities of broiler chicken gastrointestinal tract while segregating them by their preferred source of carbon. Successful execution of this novel approach would allow for significant further research potential. During this thesis a novel method for isolating anaerobic bacteria was developed. The principal idea was to microbiologically enrich gastrointestinal bacteria by culturing them on specific growth medium. Anaerobic cultivation on selective medium was performed to enrich seven different cultures. Inoculum was gastrointestinal bacteria of broiler chicken. Bacteria was cultured in liquid growth media. Growth media was otherwise identical except the difference of included carbon source. Seven different carbon sources were used to enrich bacteria that could utilize them. Substrates used were various carbohydrates, protein, fat and lactic acid. Bacteria was propagated every day, which diluted the bacterial population that could not utilize the particular substrate. Enrichment cultures were subject to short-chain fatty acid composition, ammonium concentration, and bacterial composition analysis. The novel method proved to be adequate and multiple cultures with specific characteristics were isolated. To a surprise, the genus Bacteroides was abundant in most cultures, which could be explained by the composition of used substrates. Metabolite analyses indicated features that are widely associated with bacterial utilization of each carbon source in question. The enrichment part of experiment was successful and potential for further research is significant. However, a method for treating substrates to simulate digestion of small intestine before enrichment would be advantageous.
Protein crystallization using incomplete factorial experiments.

We have studied the crystallization of Bacillus ste- arothermophilus tryptophan tRNA synthetase. Exper- imental conditions used in 35 different crystallization trials were chosen by systematic assignment of varia- bles in accordance with the two principles of randomi- zation and balance, which are characteristic of incom- plete factorial experiments. Polymorphism in the re- sulting precipitated, microcrystalline, or crystalline protein samples was identified and rated numerically on a rough but quantitative scale. Correlations between these estimates of crystal quality and all experimental variables were identified by stepwise multiple regres- sion analysis. Several variables proved to be signifi- cantly correlated with crystal quality. Having established a favorable precipitation proce- dure and ionic composition within broad limits, we next carried out a complete factorial experiment with four factors using two pH values and two temperatures in the presence or absence of two low molecular weight substrates, tryptophan and ATP. These experiments clearly established a favorable pH and produced large (0.5 mm) single crystals with each of the four possible substrate permutations. At least one crystal form, en- zyme plus tryptophan, is suitable for structural studies by x-ray diffraction. The factorial approach appears to be an advantageous alternative to classical controlled single factor and full factorial designs for establishing cause and effect relationships in protein crystallization. Rational exploration of cause and effect relationships gov- erning the crystallization of proteins has traditionally been eschewed, owing to the potentially very large number of controlled experiments required for a systematic study. The essential difficulty is that a number of different experimental conditions, pH, temperature, various mono- and divalent ions, and different organic solutes, may interact in apparently ca- pricious ways to provide a favorable environment in which crystals will eventually grow (an excellent review is Mc- Pherson, 1976a). Despite this seemingly overwhelming difficulty, small quan- tities of protein can be used quite efficiently by using the factorial approach to experimental design (Fisher, 1942). This approach is counter-intuitive: no attempt is made to identify the effects of varying individual factors by controlled experi- ments in which other factors remain constant. Rather, effi- ciency in a factorial experiment arises from two rather differ- * This work was supported by Research Grant GM21991 from the National Institutes of Health and by a fellowship in academic medi- cine from the Jefferson Pilot Corporation (C! . W. C. Jr.). The costs of publication of this article were defrayed in part by the payment of
An Example of a Simple Cache system for a Video Streaming Implementation within a Network Simulation

The modern expansion of public streaming has played a considerable part in the growth of distributed multimedia, with special reference to video. However, since the Internet is an inter-connected web of different network speeds, streaming video is still a difficult service to implement to all locations. This paper illustrates two simple simulated network streaming environments. The first models a broadcast network and the second model represents a multicast network. A simple cache system is then implemented into these models to investigate whether a significant difference exists between the cache size and the different network bandwidths of these two optimization systems. This caching system will then be used to compare the impact of videos (characterised by different resolutions and degrees of picture motion) on the cache performance.
The Role of Proteasome Inhibition With Bortezomib in the Treatment of Antibody-Mediated Rejection After Kidney-Only or Kidney-Combined Organ Transplantation

Background. We report our initial experience in using the proteasome inhibitor, bortezomib, to treat established antibody-mediated rejection (AMR) in 20 patients. Methods. There were 16 kidney-only and 4 kidney-combined organ recipients with de novo donor-specific antibody (DSA) and histologic evidence of AMR with peritubular capillaries C4d deposition. AMR was diagnosed 19.8 months (range 1-71 months) posttransplant. Patients received intravenous corticosteroids followed by a 2-week cycle on days 1-4-8-11 of plasmapheresis and 1.3 mg/m2 bortezomib; then 0.5 mg/kg intravenous immunoglobulin four times. Results. De novo class I DSA was detected in 11 (55%) and class II DSA in 18 (90%) recipients. The absolute mean difference between peak-nadir dominant DSA was 68,171 molecules of equivalent soluble fluorochrome (P<0.0001), representing 55%±22%. Only two patients (10%) had undetectable DSA after treatment. Patient survival is 100%, and graft survival is 85% with a mean follow-up of 9.8 months (range 2-20 months). The treatment was generally well tolerated but caused fatigue, gastrointestinal complaints, fluid retention, and thrombocytopenia in a number of patients. The last follow-up estimated glomerular filtration rate was 41.9±16.8 mL/min (range 20.6-72.2 mL/min). However, only 25% returned to their baseline renal function before AMR, and many have proteinuria with urine protein/creatinine more than 0.5 in 41% and more than 1.0 in 18%. Conclusions. The bortezomib-containing regimen demonstrated activity in AMR but seems to be most effective before the onset of significant renal dysfunction (serum creatinine <3 mg/dL) or proteinuria (<1 g/day). The best use of bortezomib to treat AMR should be evaluated in controlled trials using dosing strategies that include longer courses or retreatment schedules.