Miracle-dz/UniFAR-FTUs huggingface dataset:
Burst generation in rat pyramidal neurones by regenerative potentials elicited in a restricted part of the basilar dendritic tree

The common preconception about central nervous system neurones is that thousands of small postsynaptic potentials sum across the entire dendritic tree to generate substantial firing rates, previously observed in in vivo experiments. We present evidence that local inputs confined to a single basal dendrite can profoundly influence the neuronal output of layer V pyramidal neurones in the rat prefrontal cortical slices. In our experiments, brief glutamatergic stimulation delivered in a restricted part of the basilar dendritic tree invariably produced sustained plateau depolarizations of the cell body, accompanied by bursts of action potentials. Because of their small diameters, basolateral dendrites are not routinely accessible for glass electrode measurements, and very little is known about their electrical properties and their role in information processing. Voltage‐sensitive dye recordings were used to follow membrane potential transients in distal segments of basal branches during sub‐ and suprathreshold glutamate and synaptic stimulations. Recordings were obtained simultaneously from multiple dendrites and multiple points along individual dendrites, thus showing in a direct way how regenerative potentials initiate at the postsynaptic site and propagate decrementally toward the cell body. The glutamate‐evoked dendritic plateau depolarizations described here are likely to occur in conjunction with strong excitatory drive during so‐called ‘UP states’, previously observed in in vivo recordings from mammalian cortices.
The Relation of Carotid Calcium Volume with Carotid Artery Stenosis in Symptomatic Patients

Is calcium volume a surrogate marker for carotid artery stenosis? These authors explored the relationship between calcium volume and stenosis as seen on CT angiography studies. In symptomatic sides calcium volumes were not related to stenosis degrees, and in asymptomatic sides were only weakly related. Their conclusion was that calcium volume cannot be used to estimate or predict degree of stenosis even in symptomatic patients. BACKGROUND AND PURPOSE: Recent research showed a strong correlation of calcium volume scores with degree of stenosis, suggesting that calcium volume could be used in the diagnosis of carotid artery stenosis. We investigated the accuracy of the use of calcium volume scores to diagnose carotid artery stenosis in our target population of recently symptomatic patients. MATERIALS AND METHODS: Ninety symptomatic patients suspected of having carotid artery stenosis underwent CTA, resulting in images of 159 evaluable arteries. The correlation between calcium volume and degree of stenosis was calculated by using the Pearson correlation coefficient. With thresholds of 0.03 and 0.09 mL, we assessed the diagnostic performance of a calcium volume−based evaluation of stenosis for a previously reported stenosis cutoff of 40% and for the clinically important cutoffs of 50% and 70%. RESULTS: In our patients series, the calcium volume score was not related to the stenosis degree on the symptomatic side (R = 0.04, P = .7) and was weakly related on the asymptomatic side (R = 0.29, P = .005). The diagnostic accuracy of the calcium volume score to estimate 40% stenosis was relatively low: a sensitivity of 47% or 64% and a specificity of 52% or 82%, for the 0.09 and 0.03 mL thresholds, respectively. The diagnostic accuracy decreased with increasing degree of stenosis. CONCLUSIONS: We could not confirm the previously reported strong correlation of calcium volume with stenosis degree in our population of patients with recent neurologic symptoms. We conclude that in this particular domain, calcium volume cannot be used to estimate the degree of stenosis.
The inflation-hedging ability of individual shares: Evidence from the Johannesburg Stock Exchange (JSE)

ABSTRACT The erosion of purchasing power due to inflation is a source of concern for investors who invest in stocks over long investment horizons. This study examines the inflation-hedging abilities of stocks for South Africa over three different investment periods for both individual stock and for different sectors based on their inflation betas. The results indicate that inflation-hedging betas did not produce conclusive evidence of hedging benefits. A 12-month rolling regression of three long-term portfolios with high, close to zero and low betas revealed that the zero beta portfolio yielded the best average geometric real return over the 2004 to 2015 period. Measuring the inflation-hedging benefits of individual stocks and sector portfolios based on performance measures such as real return, reliability and risk-adjusted return was more conclusive. The results also suggest that some sectors such as technology, consumer staples and healthcare sectors exhibited better inflation-hedging possibilities than other sectors during unstable inflationary conditions.
Viability of primary cultured retinal neurons in a hyperglycemic condition

The retina of Wistar rats within 1–3 days of birth were dissociated into a retinal cell suspension using 0.05% trypsin digestion. The cell suspension was incubated in Dulbecco's modified Eagle's medium for 24 hours, followed by neurobasal medium for 5–7 days. Nissl staining showed that 79.86% of primary cultured retinal cells were positive and immunocytochemical staining showed that the purity of anti-neurofilament heavy chain antibody-positive cells was 71.53%, indicating that the primary culture system of rat retinal neurons was a reliable and stable cell system with neurons as the predominant cell type. The primary cultured retinal neurons were further treated with 0, 5.5, 15, 25, and 35 mM glucose for 24, 48, and 72 hours. The thiazolyl blue tetrazolium bromide test and flow cytometry showed that with increasing glucose concentration and treatment duration, the viability of retinal neurons was reduced, and apoptosis increased. In particular, 35 mM glucose exhibited the most significant effect at 72 hours. Thus, rat retinal neurons treated with 35 mM glucose for 72 hours can be used to simulate a neuronal model of diabetic retinopathy.
The Integration and Coordination of Public Policies: A Systematic Comparative Review

Abstract This article undertakes a systematic comparative review of research on policy integration and coordination. Specifically, it compares studies focusing on “policy integration” with those using “joined-up government” or “whole-of-government” as key analytical concepts. It discusses differences and similarities between the two groups of articles in terms of empirical and theoretical focus as well as research design, and concludes by suggesting that the existence of different strands of literature makes sense but more exchanges across them are both possible and welcome, so as to align organizational and policy-related factors for the analysis of the relations between policy sectors.
Tree Search Methods for Diplomacy Agents

After the defeat of the human Go champion by Artiﬁcial Intelligence (AI) methods, Diplomacy has been named among the choices for a next-to-beat game. Diplomacy is a deterministic boardgame, in which players attempt to take control over Europe. The game is considered hard because it has multiple players, simultaneous play and free communication. Our goal is to make an AI agent for Diplomacy with a very basic strategy. We performed a preliminary study to ﬁnd out if a program using tree search methods performs well in Diplomacy and whether or not it will be able to recognize good patterns. We made an agent using a basic form of Monte Carlo Tree Search (MCTS) and another using Minimax. These agents focus on the tactical decisions and ignore communications between players. Several MCTS agents, each with a diﬀerent number of playouts, are tested against each other on small simpliﬁed boards. It becomes immediately clear that Minimax is not feasible at all without pruning. This is because even for a tiny board and expanding to a limited depth the branching factor is too large. While MCTS can take considerable time to compute its moves as well, its decisions can be made well within the time limits included in the rules. Against random play MCTS managed to win most of the games, depending on the amount of playouts it performed. Furthermore, some of the strategic patterns adopted by human players were also found in the plays of the MCTS agent. The MCTS agent should be further tested in the full game (with all possible moves and with communications) and against other agents, however it is recommended to add the Upper Conﬁdence Bound heuristic to the MCTS algorithm to improve its eﬃciency.
Cerebrospinal Fluid Amyloid-β (Aβ) as an Effect Biomarker for Brain Aβ Lowering Verified by Quantitative Preclinical Analyses

Reducing the generation of amyloid-β (Aβ) in the brain via inhibition of β-secretase or inhibition/modulation of γ-secretase has been pursued as a potential disease-modifying treatment for Alzheimer's disease. For the discovery and development of β-secretase inhibitors (BACEi), γ-secretase inhibitors (GSI), and γ-secretase modulators (GSM), Aβ in cerebrospinal fluid (CSF) has been presumed to be an effect biomarker for Aβ lowering in the brain. However, this presumption is challenged by the lack of quantitative understanding of the relationship between brain and CSF Aβ lowering. In this study, we strived to elucidate how the intrinsic pharmacokinetic (PK)/pharmacodynamic (PD) relationship for CSF Aβ lowering is related to that for brain Aβ through quantitative modeling of preclinical data for numerous BACEi, GSI, and GSM across multiple species. Our results indicate that the intrinsic PK/PD relationship in CSF is predictive of that in brain, at least in the postulated pharmacologically relevant range, with excellent consistency across mechanisms and species. As such, the validity of CSF Aβ as an effect biomarker for brain Aβ lowering is confirmed preclinically. Meanwhile, we have been able to reproduce the dose-dependent separation between brain and CSF effect profiles using simulations. We further discuss the implications of our findings to drug discovery and development with regard to preclinical PK/PD characterization and clinical prediction of Aβ lowering in the brain.
Neoplastic Reprogramming of Patient‐Derived Adipose Stem Cells by Prostate Cancer Cell‐Associated Exosomes

Emerging evidence suggests that mesenchymal stem cells (MSCs) are often recruited to tumor sites but their functional significance in tumor growth and disease progression remains elusive. Herein we report that prostate cancer (PC) cell microenvironment subverts PC patient adipose‐derived stem cells (pASCs) to undergo neoplastic transformation. Unlike normal ASCs, the pASCs primed with PC cell conditioned media (CM) formed prostate‐like neoplastic lesions in vivo and reproduced aggressive tumors in secondary recipients. The pASC tumors acquired cytogenetic aberrations and mesenchymal‐to‐epithelial transition and expressed epithelial, neoplastic, and vasculogenic markers reminiscent of molecular features of PC tumor xenografts. Our mechanistic studies revealed that PC cell‐derived exosomes are sufficient to recapitulate formation of prostate tumorigenic mimicry generated by CM‐primed pASCs in vivo. In addition to downregulation of the large tumor suppressor homolog2 and the programmed cell death protein 4, a neoplastic transformation inhibitor, the tumorigenic reprogramming of pASCs was associated with trafficking by PC cell‐derived exosomes of oncogenic factors, including H‐ras and K‐ras transcripts, oncomiRNAs miR‐125b, miR‐130b, and miR‐155 as well as the Ras superfamily of GTPases Rab1a, Rab1b, and Rab11a. Our findings implicate a new role for PC cell‐derived exosomes in clonal expansion of tumors through neoplastic reprogramming of tumor tropic ASCs in cancer patients. Stem Cells 2014;32:983–997
Diversity of The Chlorite Dismutase Gene in Low and High Organic Carbon Rhizosphere Soil Colonized by Perchlorate-Reducing Bacteria

Chlorite dismutase (cld) is an essential enzyme in the biodegradation of perchlorate. The objective of this study was to determine the change in sequence diversity of the cld gene, and universal bacterial 16S rRNA genes, in soil samples under varying conditions of organic carbon, bioaugmentation, and plant influence. The cld gene diversity was not different between high organic carbon (HOC) and low organic carbon (LOC) soil. Combining results from HOC and LOC soil, diversity of the cld gene was decreased in soil that had been bioaugmented or planted. However, with both bioaugmentation and planting the cld diversity was not decreased. These observations were repeated when focusing on LOC soil. However, in HOC soil the cld diversity was not affected by reactor treatment. General bacterial diversity as measured with 16S rRNA was significantly greater in HOC soil than in LOC soil, but no significant difference was observed between reference soil and planted or bioaugmented soil. Different sequences of the cld gene occur in different species of microorganisms. In LOC soil, combining bioaugmentation and planting results in a highly diverse population of perchlorate degraders. This diverse population will be more resilient and is desirable where perchlorate reduction is a critical remediation process. Supplemental materials are available for this article. Go to the publisher's online edition of International Journal of Phytoremediation to view the supplemental file.
A Theory of Bank Illiquidity and Default with Hidden Trades

I develop a theory of financial intermediation to explore how the availability of trading opportunities affects the link between the liquidity of financial institutions and their default decisions. In it, banks hedge against liquidity shocks either in the interbank market or by using a costly bankruptcy procedure, and depositors trade in the asset market without being observed. In this environment, the competitive pressure from the asset markets makes intermediaries choose an illiquid asset portfolio. I prove three results. First, illiquid banks default in equilibrium only when there is systemic risk and an unpredicted crisis hits the economy. Second, in contrast to the previous literature, the allocation at default is not socially optimal. Third, the constrained efficient allocation can be decentralized with the introduction of countercyclical liquidity requirements.
Plasmin-induced procoagulant effects in the blood coagulation: a crucial role of coagulation factors V and VIII

Plasminogen activators provide effective treatment for patients with acute myocardial infarction. However, paradoxical elevation of thrombin activity associated with failure of clot lysis and recurrent thrombosis has been reported. Generation of thrombin in these circumstances appears to be owing to plasmin (Plm)-induced activation of factor (F) XII. Plm catalyzes proteolysis of several coagulant factors, but the roles of these factors on Plm-mediated procoagulant activity remain to be determined. Recently developed global coagulation assays were used in this investigation. Rotational thromboelastometry using whole blood, clot waveform analysis and thrombin generation tests using plasma, showed that Plm (≥125 nmol/l) shortened the clotting times in similar dose-dependent manners. In particular, the thrombin generation test, which was unaffected by products of fibrinolysis, revealed the enhanced coagulation with a ∼two-fold increase of peak level of thrombin generation. Studies using α2-antiplasmin-deficient plasma revealed that much lower dose of Plm (≥16 nmol/l) actually contributed to enhancing thrombin generation. The shortening of clotting time could be observed even in the presence of corn trypsin inhibitor, supporting that Plm exerted the procoagulant activity independently of FXII. In addition, using specific coagulation-deficient plasmas, the clot waveform analysis showed that Plm did not shorten the clotting time in only FV-deficient or FVIII-deficient plasma in prothrombin time-based or activated partial thromboplastin time-based assay, respectively. Our results indicated that Plm did possess procoagulant activity in the blood coagulation, and this effect was likely attributed by multicoagulation factors, dependent on FV and/or FVIII.
Maternal Smoking Among Women With and Without Use of Assisted Reproductive Technologies.

OBJECTIVE To estimate smoking prevalence during the year before pregnancy and during pregnancy and adverse outcomes among women who delivered infants with and without assisted reproductive technology (ART) using linked birth certificates (BC) and National ART Surveillance System (NASS) data. METHODS Data were analyzed for 384,390 women and 392,248 infants born in Massachusetts and Michigan during 2008-2009. Maternal smoking prevalence was estimated using smoking indicated from BC by ART status. For ART users, to evaluate underreporting, prepregnancy smoking was estimated from BC, NASS, or both sources. Effect of prenatal smoking on preterm and mean birthweight (term only) for singleton infants were examined by ART status. RESULTS Maternal smoking prevalence estimates were significantly lower for ART users than nonusers (prepregnancy = 3.2% vs. 16.7%; prenatal = 1.0% vs. 11.1%, p < 0.05). When combining smoking information from BC and NASS, prepregnancy smoking prevalence estimates for ART users could be as high as 4.4% to 6.1%. Adverse effects of smoking on infant outcomes in ART pregnancies were consistent with the effects seen in non-ART pregnancies, specifically decline in infant birthweight and increase in preterm delivery, although association between smoking and preterm was not significant. CONCLUSION A low, but substantial proportion of ART users smoked before and during pregnancy. As ART users are highly motivated to get pregnant, it should be clearly communicated that smoking can decrease fertility and adversely affect pregnancy outcomes. Continued efforts are needed to encourage smoking cessation and maintain tobacco abstinence among all women of reproductive age.
A New Design of $H$ -Infinity Piecewise Filtering for Discrete-Time Nonlinear Time-Varying Delay Systems via T–S Fuzzy Affine Models

This paper proposes a novel delay-dependent approach to the piecewise-affine <inline-formula> <tex-math notation="LaTeX">$\boldsymbol {H}$ </tex-math></inline-formula>-infinity filter design for discrete-time state-delayed nonlinear systems. The nonlinear plant is expressed by a Takagi–Sugeno fuzzy-affine model and the state delay is considered to be time-varying with available lower and upper bounds. The purpose is to design an admissible filter that guarantees the asymptotic stability of the resulting filtering error system (FES) with a prescribed disturbance attenuation level in an <inline-formula> <tex-math notation="LaTeX">$\boldsymbol {H}$ </tex-math></inline-formula>-infinity sense. By applying a new piecewise-fuzzy Lyapunov–Krasovskii functional, combined with a novel summation inequality, improved reciprocally convex inequality and <inline-formula> <tex-math notation="LaTeX">$\boldsymbol {S}$ </tex-math></inline-formula>-procedure, the <inline-formula> <tex-math notation="LaTeX">$\boldsymbol {H}$ </tex-math></inline-formula>-infinity performance analysis criterion is first developed for the FES. Furthermore, the filter synthesis is carried out by some elegant convexification techniques. Finally, simulation examples are employed to confirm the effectiveness and less conservatism of the proposed methods.
ARGONAUTE 6 bridges transposable element mRNA‐derived siRNAs to the establishment of DNA methylation

Transposable elements (TEs) generate mutations and chromosomal instability when active. To repress TE activity, eukaryotic cells evolved mechanisms to both degrade TE mRNAs into small interfering RNAs (siRNAs) and modify TE chromatin to epigenetically inhibit transcription. Since the populations of small RNAs that participate in TE post‐transcriptional regulation differ from those that establish RNA‐directed DNA methylation (RdDM), the mechanism through which transcriptionally active TEs transition from post‐transcriptional RNAi regulation to chromatin level control has remained unclear. We have identified the molecular mechanism of a plant pathway that functions to direct DNA methylation to transcriptionally active TEs. We demonstrated that 21–22 nucleotide (nt) siRNA degradation products from the RNAi of TE mRNAs are directly incorporated into the ARGONAUTE 6 (AGO6) protein and direct AGO6 to TE chromatin to guide its function in RdDM. We find that this pathway functions in reproductive precursor cells to primarily target long centromeric high‐copy transcriptionally active TEs for RdDM prior to gametogenesis. This study provides a direct mechanism that bridges the gap between the post‐transcriptional regulation of TEs and the establishment of TE epigenetic silencing.
Comparison of the limulus amebocyte lysate test and gas chromatography-mass spectrometry for measuring lipopolysaccharides (endotoxins) in airborne dust from poultry-processing industries

The lipopolysaccharide (endotoxin) content in airborne dust samples from three different poultry slaughterhouses was determined with both the chromogenic Limulus amebocyte lysate assay and gas chromatography-mass spectrometry analysis of lipopolysaccharide-derived 3-hydroxy fatty acids. Gram-negative cell walls were also measured by using two-dimensional gas chromatography/electron-capture analysis of diaminopimelic acid originating from the peptidoglycan. The correlation between the results of the Limulus assay and those of gas chromatography-mass spectrometry for determination of the lipopolysaccharide content in the dust samples was poor, whereas a good correlation was obtained between lipopolysaccharide and diaminopimelic acid concentrations with the gas chromatographic methods. The results suggest that it is predominantly cell-wall-dissociated lipopolysaccharides that are measured with the Limulus assay, whereas the gas chromatographic methods allow determination of total concentrations of lipopolysaccharide, including Limulus-inactive lipopolysaccharide, gram-negative cells, and cellular debris.
Quantification of Staphylococcus aureus and Staphylococcus epidermidis on the hands of health‐care workers using a real‐time polymerase chain reaction method

Objective. The objective of this study was to test a polymerase chain reaction (PCR) assay intended as a tool for monitoring hand hygiene in hospital wards. Methods. The hands of 20 health‐care workers were sampled for 10 days using real‐time PCR for quantification of Staphylococcus aureus and S. epidermidis. Reference intervals (CI) and biological variation were evaluated using index of individuality (II) and critical difference (CD). Results. 45% of the participants were positive for S. aureus on all 10 days. Intra‐individual biological variation (CVI) was 129% for S. aureus and 62% for S. epidermidis. Inter‐individual biological variation (CVG) was 245% for S. aureus and 107% for S. epidermidis. II was 0.55 for S. aureus and 0.71 for S. epidermidis, indicating a high degree of individuality and limited use of the reference values. A significant individual change was determined at 374% for S. aureus and 211% for S. epidermidis. In an intervention study aimed at better hand hygiene in a ward with n participants, the difference before and after intervention is significant at CDI/√n per cent. Conclusions. The PCR assay can be used to detect change in a group mean of S. aureus and S. epidermidis in a hospital ward, i.e. before and after an intervention to improve hand hygiene. For the individual, the change in bacteria levels needed for significance is compromised by high intra‐individual variation.