Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of the Human ST6GalNAc-I and ST6GalNAc-II in the Synthesis of the Cancer-Associated Sialyl-Tn Antigen

The Sialyl-Tn antigen (Neu5Acα2–6GalNAc-O-Ser/Thr) is highly expressed in several human carcinomas and is associated with carcinoma aggressiveness and poor prognosis. We characterized two human sialyltransferases, CMP-Neu5Ac:GalNAc-R α2,6-sialyltransferase (ST6GalNAc)-I and ST6GalNAc-II, that are candidate enzymes for Sialyl-Tn synthases. We expressed soluble recombinant hST6GalNAc-I and hST6GalNAc-II and characterized the substrate specificity of both enzymes toward a panel of glycopeptides, glycoproteins, and other synthetic glycoconjugates. The recombinant ST6GalNAc-I and ST6GalNAc-II showed similar substrate specificity toward glycoproteins and GalNAcα-O-Ser/Thr glycopeptides, such as glycopeptides derived from the MUC2 mucin and the HIVgp120. We also observed that the amino acid sequence of the acceptor glycopeptide contributes to the in vitro substrate specificity of both enzymes. We additionally established a gastric cell line, MKN45, stably transfected with the full length of either ST6GalNAc-I or ST6GalNAc-II and evaluated the carbohydrate antigens expression profile induced by each enzyme. MKN45 transfected with ST6GalNAc-I showed high expression of Sialyl-Tn, whereas MKN45 transfected with ST6GalNAc-II showed the biosynthesis of the Sialyl-6T structure [Galβ1–3 (Neu5Acα2–6)GalNAc-O-Ser/Thr]. In conclusion, although both enzymes show similar in vitro activities when Tn antigen alone is available, whenever both Tn and T antigens are present, ST6GalNAc-I acts preferentially on Tn antigen, whereas the ST6GalNAc-II acts preferentially on T antigen. Our results show that ST6GalNAc-I is the major Sialyl-Tn synthase and strongly support the hypothesis that the expression of the Sialyl-Tn antigen in cancer cells is due to ST6GalNAc-I activity.
The Superior Olivary Nucleus and Its Influence on Nucleus Laminaris: A Source of Inhibitory Feedback for Coincidence Detection in the Avian Auditory Brainstem

Located in the ventrolateral region of the avian brainstem, the superior olivary nucleus (SON) receives inputs from nucleus angularis (NA) and nucleus laminaris (NL) and projects back to NA, NL, and nucleus magnocellularis (NM). The reciprocal connections between the SON and NL are of particular interest because they constitute a feedback circuit for coincidence detection. In the present study, the chick SON was investigated. In vivo tracing studies show that the SON projects predominantly to the ipsilateral NM, NL, and NA.In vitro whole-cell recording reveals single-cell morphology, firing properties, and postsynaptic responses. SON neurons are morphologically and physiologically suited for temporal integration; their firing patterns do not reflect the temporal structure of their excitatory inputs. Of most interest, direct stimulation of the SON evokes long-lasting inhibition in NL neurons. The inhibition blocks both intrinsic spike generation and orthodromically evoked activity in NL neurons and can be eliminated by bicuculline methiodide, a potent antagonist for GABAAreceptor-mediated neurotransmission. These results strongly suggest that the SON provides GABAergic inhibitory feedback to laminaris neurons. We discuss a mechanism whereby SON-evoked GABAergic inhibition can influence the coding of interaural time differences for sound localization in the avian auditory brainstem.
Elevated Plasma Von Willebrand Factor and Propeptide Levels in Malawian Children with Malaria

Background In spite of the significant mortality associated with Plasmodium falciparum infection, the mechanisms underlying severe disease remain poorly understood. We have previously shown evidence of endothelial activation in Ghanaian children with malaria, indicated by elevated plasma levels of both von Willebrand factor (VWF) and its propeptide. In the current prospective study of children in Malawi with retinopathy confirmed cerebral malaria, we compared these markers with uncomplicated malaria, non malarial febrile illness and controls. Methods and Findings Children with cerebral malaria, mild malaria and controls without malaria were recruited into the study. All comatose patients were examined by direct and indirect ophthalmoscopy. Plasma VWF and propeptide levels were measured by ELISA. Median VWF and propeptide levels were significantly higher in patients with uncomplicated malaria than in children with non-malarial febrile illness of comparable severity, in whom levels were higher than in non-febrile controls. Median concentrations of both markers were higher in cerebral malaria than in uncomplicated malaria, and were similar in patients with and without retinopathy. Levels of both VWF and propeptide fell significantly 48 hours after commencing therapy and were normal one month later. Conclusions In children with malaria plasma VWF and propeptide levels are markedly elevated in both cerebral and mild paediatric malaria, with levels matching disease severity, and these normalize upon recovery. High levels of both markers also occur in retinopathy-negative ‘cerebral malaria’ cases, many of whom are thought to be suffering from diseases other than malaria, indicating that further studies of these markers will be required to determine their sensitivity and specificity.
Effects of a ketogenic diet on hippocampal plasticity in freely moving juvenile rats

Ketogenic diets are low‐carbohydrate, sufficient protein, high‐fat diets with anticonvulsant activity used primarily as a treatment for pediatric epilepsy. The anticonvulsant mechanism is thought to involve elevating inhibition and/or otherwise limiting excitability in the brain. Such a mechanism, however, might also significantly affect normal brain activity and limit synaptic plasticity, effects that would be important to consider in the developing brain. To assess ketogenic diet effects on synaptic transmission and plasticity, electrophysiological recordings were performed at the perforant path/dentate gyrus synapse in awake, freely‐behaving juvenile male rats. Electrodes were implanted 1 week prior to recording. Animals were fed regular chow or a ketogenic diet ad libitum for 3 weeks before recording. Although the ketogenic diet did not significantly alter baseline excitability (assessed by input–output curves) or short‐term plasticity (using the paired‐pulse ratio), it did reduce the magnitude of long‐term potentiation at all poststimulation timepoints out to the last time measured (48 h). The results suggest an effect of ketogenic diet‐feeding on the induction magnitude but not the maintenance of long‐term potentiation. The lack of effect of the diet on baseline transmission and the paired‐pulse ratio suggests a mechanism that limits excitation preferentially in conditions of strong stimulation, consonant with clinical reports in which the ketogenic diet alleviates seizures without a major impact on normal brain activity. Limiting plasticity in a seizure‐susceptible network may limit seizure‐induced epileptogenesis which may subserve the ongoing benefit of the ketogenic diet in epilepsy.
The effect of waves on subgrid-scale stresses, dissipation and model coefficients in the coastal ocean bottom boundary layer

Six sets of particle image velocimetry (PIV) data from the bottom boundary layer of the coastal ocean are examined. The data represent periods of high, moderate and weak mean flow relative to the amplitude of wave-induced motion, which correspond to high, moderate and low Reynolds numbers based on the Taylor microscale (Re). The two-dimensional PIV velocity distributions enable spatial filtering to calculate some of the subgrid-scale (SGS) stresses, from which we can estimate the SGS dissipation, and evaluate the performance of typically used SGS stress models. The previously reported mismatch between the SGS and viscous dissipation at moderate and low Reynolds numbers appears to be related to the sparsity of large vortical structures that dominate energy fluxes. Conditional sampling of SGS stresses and dissipation based on wave phase using Hilbert transforms demonstrate persistent and repeatable direct effects of large-scale but weak straining by the waves on the SGS energy flux at small scales. The SGS energy flux is phase-dependent, peaking when the streamwise-wave-induced velocity is accelerating, and lower when this velocity is decelerating. Combined with strain rate generated by the mean flow, the streamwise wave strain causes negative energy flux (backscatter), whereas the vertical wave strain causes a positive flux. The phase-dependent variations and differences between horizontal and vertical contributions to the cascading process extend to strains that are substantially higher than the wave-induced motion. These trends may explain the measured difference between spatial energy spectra of streamwise velocity fluctuations and spectra of the wall-normal component, i.e. the formation of spectral bumps in the spectra of the streamwise component at the wavenumbers for the transition between inertial and dissipation scales. All the model coefficients of typical SGS stress models measured here are phase dependent and show similar trends. Thus, the variations of measured SGS dissipation with phase are larger than those predicted by the model variables. In addition, the measured coefficients of the static Smagorinsky SGS stress model decrease with decreasing turbulence levels, and increase with filter size. The dynamic model provides higher correlation coefficients than the Smagorinsky model, but the substantial fluctuations in their values indicate that ensemble averaging is required. The ‘global’ dynamic model coefficients indicate that the use of a scale-dependent dynamic model may be appropriate. The structure function model yields poor correlation coefficients and is found to be over-dissipative under all but the highest turbulence levels. The nonlinear model has higher correlations with measured stresses, as expected, but it also does not reproduce the trends with wave phase.
Keep an Eye on PPi: The Vacuolar-Type H+-Pyrophosphatase Regulates Postgerminative Development in Arabidopsis[C][W][OA]

Oilseed germination requires gluconeogenesis, the conversion of storage lipids into carbohydrates, to sustain seedling heterotrophic growth. Pyrophosphate (PPi), a byproduct of ATP hydrolysis, is released by active metabolism in imbibed seeds. We report that the removal of PPi by plant vacuolar H+-pyrophosphatase is central for successful gluconeogenesis and resumption of postembryonic growth. Postgerminative growth of seed plants requires specialized metabolism, such as gluconeogenesis, to support heterotrophic growth of seedlings until the functional photosynthetic apparatus is established. Here, we show that the Arabidopsis thaliana fugu5 mutant, which we show to be defective in AVP1 (vacuolar H+-pyrophosphatase), failed to support heterotrophic growth after germination. We found that exogenous supplementation of Suc or the specific removal of the cytosolic pyrophosphate (PPi) by the heterologous expression of the cytosolic inorganic pyrophosphatase1 (IPP1) gene from budding yeast (Saccharomyces cerevisiae) rescued fugu5 phenotypes. Furthermore, compared with the wild-type and AVP1Pro:IPP1 transgenic lines, hypocotyl elongation in the fugu5 mutant was severely compromised in the dark but recovered upon exogenous supply of Suc to the growth media. Measurements revealed that the peroxisomal β-oxidation activity, dry seed contents of storage lipids, and their mobilization were unaffected in fugu5. By contrast, fugu5 mutants contained ~2.5-fold higher PPi and ~50% less Suc than the wild type. Together, these results provide clear evidence that gluconeogenesis is inhibited due to the elevated levels of cytosolic PPi. This study demonstrates that the hydrolysis of cytosolic PPi, rather than vacuolar acidification, is the major function of AVP1/FUGU5 in planta. Plant cells optimize their metabolic function by eliminating PPi in the cytosol for efficient postembryonic heterotrophic growth.
OCL2FOL+: Coping with Undefinedness

At present, the OCL language includes two constants, null and invalid, to represent undefinedness. This effectively turns OCL into a four-valued logic. It makes also problematic its mapping to first-order logic and, as a consequence, hinders the use of first-order automated-reasoning tools for OCL reasoning. We address this problem and propose a solution, grounded on the same principles underlying OCL2FOL, in order to cope with undefinedness in OCL.
Identification of buried victims in natural disaster with GPR method

Indonesian is one of the most seismically active regions in the world and has very complicated plate convergence because there is meeting point of several tectonic plates. The complexity of tectonic features causes a lot of natural disasters such as landslides, tsunamis, earth quakes, volcanoes eruption, etc. Sometimes, the disasters occurs in high populated area and causing thousands to millions of victim been buried under the rumble. Unfortunately, the evacuation still uses the conventional method such using rescue dogs whereas the sensitivity of smell is decrease when the victims buried under the level of the ground. The purpose of this study is to detect buried bodies using GPR method, so it can enhance the effectiveness and the efficiency in looking for the disaster victims. GPR method is used because it can investigate things under the ground. A detailed GPR research has been done in Cikutra Graveyard, Bandung, with corpse buried two week until two years before the research. The radar profiles from this research showed amplitude contras anomaly between the new corpse and the old ones. We obtained the amplitude contras at 1.2-1.4 meters under the surface. This method proved to be effective but still need more attention on undulated surface and non-soil areas.Indonesian is one of the most seismically active regions in the world and has very complicated plate convergence because there is meeting point of several tectonic plates. The complexity of tectonic features causes a lot of natural disasters such as landslides, tsunamis, earth quakes, volcanoes eruption, etc. Sometimes, the disasters occurs in high populated area and causing thousands to millions of victim been buried under the rumble. Unfortunately, the evacuation still uses the conventional method such using rescue dogs whereas the sensitivity of smell is decrease when the victims buried under the level of the ground. The purpose of this study is to detect buried bodies using GPR method, so it can enhance the effectiveness and the efficiency in looking for the disaster victims. GPR method is used because it can investigate things under the ground. A detailed GPR research has been done in Cikutra Graveyard, Bandung, with corpse buried two week until two years before the research. The radar profiles from .
How citation distortions create unfounded authority: analysis of a citation network

Objective To understand belief in a specific scientific claim by studying the pattern of citations among papers stating it. Design A complete citation network was constructed from all PubMed indexed English literature papers addressing the belief that β amyloid, a protein accumulated in the brain in Alzheimer’s disease, is produced by and injures skeletal muscle of patients with inclusion body myositis. Social network theory and graph theory were used to analyse this network. Main outcome measures Citation bias, amplification, and invention, and their effects on determining authority. Results The network contained 242 papers and 675 citations addressing the belief, with 220 553 citation paths supporting it. Unfounded authority was established by citation bias against papers that refuted or weakened the belief; amplification, the marked expansion of the belief system by papers presenting no data addressing it; and forms of invention such as the conversion of hypothesis into fact through citation alone. Extension of this network into text within grants funded by the National Institutes of Health and obtained through the Freedom of Information Act showed the same phenomena present and sometimes used to justify requests for funding. Conclusion Citation is both an impartial scholarly method and a powerful form of social communication. Through distortions in its social use that include bias, amplification, and invention, citation can be used to generate information cascades resulting in unfounded authority of claims. Construction and analysis of a claim specific citation network may clarify the nature of a published belief system and expose distorted methods of social citation.
quilibrium of the simultaneous etherification of sobutene and isoamylenes with ethanol in iquid-phase

The simultaneous etherification of isobutene and isoamylenes with ethanol has been studied using macroreticular acid ion-exchange resins as catalyst. Most of the experiments were carried out over Amberlyst-35. In addition, Amberlyst-15 and Purolite CT-275 were also tested. Chemical equilibrium of four chemical reactions was studied: ethyl tert-butyl ether formation, tert-amyl ethyl ether formation from isoamylenes (2-methyl-1-butene and 2-methyl2-butene) and isomerization reaction between both isoamylenes. Equilibrium data were obtained in a batchwise stirred tank reactor operated at 2.0 MPa and within the temperature range from 323 to 353 K. Experimental molar standard enthalpy and entropy changes of reaction were determined for each reaction. From these data, the molar enthalpy change of formation of ethyl tert-butyl ether and tert-amyl ethyl ether were estimated. Besides, the chemical equilibrium between both diisobutene dimers, 2,4,4-trimethyl-1-pentene and 2,4,4-trimethyl-2-pentene, was evaluated. A good agreement between thermodynamic results for the simultaneous etherification carried out in this work and those obtained for the isolated ethyl tert-butyl ether and tert-amyl ethyl ether systems was obtained. © 2013 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
Hypotheses relating to the function of the claustrum

This paper presents a new hypothesis as to the function of the claustrum. Our basic premise is that the claustrum functions as a detector and integrator of synchrony in the axonal trains in its afferent inputs. In the first place an unexpected stimulus sets up a processed signal to the sensory cortex that initiates a focus of synchronized gamma oscillations therein. This focus may then interact with a general alerting signal conveyed from the reticular formation via cholinergic mechanisms, and with other salient activations set up by the stimulus in other sensory pathways that are relayed to the cortex. This activity is relayed from the cortex to the claustrum, which then processes these several inputs by means of multiple competitive intraclaustral synchronized oscillations at different frequencies. Finally it modulates the synchronized outputs that the claustrum distributes to most cortical and many subcortical structures, including the motor cortex. In this way, during multicenter perceptual and cognitive operations, reverberating claustro-cortical loops potentiate weak intracortical synchronizations by means of connected strong intraclaustral synchronizations. These may also occur without a salient stimulus. By this mechanism, the claustrum may play a strong role in the control of interactive processes in different parts of the brain, and in the control of voluntary behavior. These may include the neural correlates of consciousness. We also consider the role of GABAergic mechanisms and deafferentation plasticity.
Expansion of the Protein Repertoire in Newly Explored Environments: Human Gut Microbiome Specific Protein Families

The microbes that inhabit particular environments must be able to perform molecular functions that provide them with a competitive advantage to thrive in those environments. As most molecular functions are performed by proteins and are conserved between related proteins, we can expect that organisms successful in a given environmental niche would contain protein families that are specific for functions that are important in that environment. For instance, the human gut is rich in polysaccharides from the diet or secreted by the host, and is dominated by Bacteroides, whose genomes contain highly expanded repertoire of protein families involved in carbohydrate metabolism. To identify other protein families that are specific to this environment, we investigated the distribution of protein families in the currently available human gut genomic and metagenomic data. Using an automated procedure, we identified a group of protein families strongly overrepresented in the human gut. These not only include many families described previously but also, interestingly, a large group of previously unrecognized protein families, which suggests that we still have much to discover about this environment. The identification and analysis of these families could provide us with new information about an environment critical to our health and well being.
Inducible Conditional Vascular-Specific Overexpression of Peroxisome Proliferator-Activated Receptor Beta/Delta Leads to Rapid Cardiac Hypertrophy

Peroxisome proliferator-activated receptors are nuclear receptors which function as ligand-activated transcription factors. Among them, peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) is highly expressed in the heart and thought to have cardioprotective functions due to its beneficial effects in metabolic syndrome. As we already showed that PPARβ/δ activation resulted in an enhanced cardiac angiogenesis and growth without impairment of heart function, we were interested to determine the effects of a specific activation of PPARβ/δ in the vasculature on cardiac performance under normal and in chronic ischemic heart disease conditions. We analyzed the effects of a specific PPARβ/δ overexpression in endothelial cells on the heart using an inducible conditional vascular-specific mouse model. We demonstrate that vessel-specific overexpression of PPARβ/δ induces rapid cardiac angiogenesis and growth with an increase in cardiomyocyte size. Upon myocardial infarction, vascular overexpression of PPARβ/δ, despite the enhanced cardiac vessel formation, does not protect against chronic ischemic injury. Our results suggest that the proper balance of PPARβ/δ activation in the different cardiac cell types is required to obtain beneficial effects on the outcome in chronic ischemic heart disease.
The Cardioprotective Effect of Hypertonic Saline Is Associated with Inhibitory Effect on Macrophage Migration Inhibitory Factor in Sepsis

Sepsis can cause myocardial dysfunction, which contributes to the high mortality of sepsis. Hypertonic saline (HS) has been reported to increase myocardial contractility in sepsis. In the present study, mechanisms of action of HS resuscitation (4 mL of 7.5% NaCl per kilogram) on cardiac function have been evaluated in septic rats. HS was administered 1 h after LPS (10 mg/kg, i.v.) challenge. The mean arterial blood pressure significantly decreased 4 h after LPS challenge, and septic shock was observed at the end of experiment (6 h). Posttreatment with HS prevented hypotension caused by LPS and significantly improved cardiac function, evidenced by increases in left ventricular developed pressure, mean +dP/dt and −dP/dt. The amplitude of electrical-stimulated intracellular Ca2+ transient in isolated single cardiomyocytes was significantly reduced after 6 h LPS insult, which was recovered by HS. In addition, LPS resulted in significant increases in neutrophil myeloperoxidase activity, macrophage migration inhibitory factor (MIF), and NF-κB phospho-p65 protein levels in myocardium at 6 h, which were significantly attenuated by HS. In conclusion, HS improved myocardial contractility and prevented circulatory failure induced by endotoxemia, which may attribute to improvement of intracellular calcium handling process and inhibitory effects on neutrophil infiltration and MIF production in hearts.