Miracle-dz/UniFAR-FTUs huggingface dataset:
Ionic Regulatory Properties of Brain and Kidney Splice Variants of the Ncx1 Na+–Ca2+ Exchanger

Ion transport and regulation of Na+–Ca2+ exchange were examined for two alternatively spliced isoforms of the canine cardiac Na+–Ca2+ exchanger, NCX1.1, to assess the role(s) of the mutually exclusive A and B exons. The exchangers examined, NCX1.3 and NCX1.4, are commonly referred to as the kidney and brain splice variants and differ only in the expression of the BD or AD exons, respectively. Outward Na+–Ca2+ exchange activity was assessed in giant, excised membrane patches from Xenopus laevis oocytes expressing the cloned exchangers, and the characteristics of Na+ i- (i.e., I1) and Ca2+ i- (i.e., I2) dependent regulation of exchange currents were examined using a variety of experimental protocols. No remarkable differences were observed in the current–voltage relationships of NCX1.3 and NCX1.4, whereas these isoforms differed appreciably in terms of their I1 and I2 regulatory properties. Sodium-dependent inactivation of NCX1.3 was considerably more pronounced than that of NCX1.4 and resulted in nearly complete inhibition of steady state currents. This novel feature could be abolished by proteolysis with α-chymotrypsin. It appears that expression of the B exon in NCX1.3 imparts a substantially more stable I1 inactive state of the exchanger than does the A exon of NCX1.4. With respect to I2 regulation, significant differences were also found between NCX1.3 and NCX1.4. While both exchangers were stimulated by low concentrations of regulatory Ca2+ i, NCX1.3 showed a prominent decrease at higher concentrations (>1 μM). This does not appear to be due solely to competition between Ca2+ i and Na+ i at the transport site, as the Ca2+ i affinities of inward currents were nearly identical between the two exchangers. Furthermore, regulatory Ca2+ i had only modest effects on Na+ i-dependent inactivation of NCX1.3, whereas I1 inactivation of NCX1.4 could be completely eliminated by Ca2+ i. Our results establish an important role for the mutually exclusive A and B exons of NCX1 in modulating the characteristics of ionic regulation and provide insight into how alternative splicing tailors the regulatory properties of Na+–Ca2+ exchange to fulfill tissue-specific requirements of Ca2+ homeostasis.
Reelin, Very-Low-Density Lipoprotein Receptor, and Apolipoprotein E Receptor 2 Control Somatic NMDA Receptor Composition during Hippocampal Maturation In Vitro

Reelin is a secreted protein that regulates brain layer formation during embryonic development. Reelin binds several receptors, including two members of the low-density lipoprotein (LDL) receptor family, the apolipoprotein E receptor 2 (ApoER2) and the very-low-density lipoprotein receptor (VLDLR). Despite the high level of expression of Reelin and ApoER2 in the postnatal brain, their functions in the adult CNS remain elusive. Here, using electrophysiological, immunocytochemical, and biochemical approaches in cultured postnatal hippocampal neurons, we show that Reelin controls the change in subunit composition of somatic NMDA glutamate receptors (NMDARs) during maturation. We found that maturation is characterized by the gradual decrease of the participation of NR1/2B receptors to whole-cell NMDAR-mediated currents. This maturational change was mirrored by a timely correlated increase of both Reelin immunoreactivity in neuronal somata and the amount of secreted Reelin. Chronic blockade of the function of Reelin with antisense oligonucleotides or the function-blocking antibody CR-50 prevented the decrease of NR1/2B-mediated whole-cell currents. Conversely, exogenously added recombinant Reelin accelerated the maturational changes in NMDA-evoked currents. The maturation-induced change in NMDAR subunits also was blocked by chronic treatment with an inhibitor of the Src kinase signaling pathway or an antagonist of the LDL receptors, but not by inhibitors of another class of Reelin receptor belonging to the integrin family. Consistent with these results, immunocytochemistry revealed that NR1-expressing neurons also expressed ApoER2 and VLDLR. These data reveal a new role for Reelin and LDL receptors and reinforce the idea of a prominent role of extracellular matrix proteins in postnatal maturation.
Fluoro-Jade: Novel Fluorochromes for Detecting Toxicant-Induced Neuronal Degeneration

Two anionic fluorescein derivatives can be used for the simple and definitive localization of neuronal degeneration in brain tissue sections. Initial work on the first generation fluorochrome, Fluoro-Jade, demonstrated the utility of this compound for the detection of neuronal degeneration induced by a variety of well-characterized neurotoxicants, including kainic acid, 3-nitropropionic acid, isoniazid, ibogaine, domoic acid, and dizocilpine maleate (MK-801). After validation, the tracer was used to reveal previously unreported sites of neuronal degeneration associated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), methamphetamine, and d-fenfluramine. Preliminary findings with a second generation fluorescein derivative, Fluoro-Jade B, suggest that this tracer results in staining of optimal contrast and resolution in animals dosed with kainic acid. These 2 tracers can be combined with other histologic methods, including immunofluoresence and fluorescent Nissl stains. Recent preliminary findings on a number of specialized applications of Fluoro-Jade include the detection of apoptosis, amyloid plaques, astrocytes, and dead cells in tissue culture.
Application of Dual Phase Imaging of 11C-Acetate Positron Emission Tomography on Differential Diagnosis of Small Hepatic Lesions

Objective Previously we observed that dual phase 11C-acetate positron emission tomography (AC-PET) could be employed for differential diagnosis of liver malignancies. In this study, we prospectively evaluated the effect of dual phase AC-PET on differential diagnosis of primary hepatic lesions of 1–3 cm in size. Methods 33 patients having primary hepatic lesions with size of 1–3 cm in diameter undertook dual phase AC-PET scans. Procedure included an early upper-abdomen scan immediately after tracer injection and a conventional scan in 11–18 min. The standardized uptake value (SUV) was calculated for tumor (SUVT) and normal tissue (SUVB), from which 11C-acetate uptake ratio (as lesion against normal liver tissue, SUVT/SUVB) in early imaging (R1), conventional imaging (R2), and variance between R2 and R1 (ΔR) were derived. Diagnoses based on AC-PET data and histology were compared. Statistical analysis was performed with SPSS 19.0. Results 20 patients were found to have HCC and 13 patients had benign tumors. Using ΔR>0 as criterion for malignancy, the accuracy and specificity were significantly increased comparing with conventional method. The area under ROC curve (AUC) for R1, R2, and ΔR were 0.417, 0.683 and 0.831 respectively. Differential diagnosis between well-differentiated HCCs and benign lesions of FNHs and hemangiomas achieved 100% correct. Strong positive correlation was also found between R1 and R2 in HCC (r2 = 0.55, P<0.001). Conclusions Dual phase AC-PET scan is a useful procedure for differential diagnosis of well-differentiated hepatocellular carcinoma and benign lesions. The dynamic changes of 11C-acetate uptake in dual phase imaging provided key information for final diagnosis.
Associations between initial antimicrobial therapy and medical outcomes for hospitalized elderly patients with pneumonia.

BACKGROUND Although medical practice guidelines exist, there have been no large-scale studies assessing the relationship between initial antimicrobial therapy and medical outcomes for patients hospitalized with pneumonia. OBJECTIVE To determine the associations between initial antimicrobial therapy and 30-day mortality for these patients. METHODS Hospital records for 12945 Medicare inpatients (> or = 65 years of age) with pneumonia were reviewed. Associations between initial antimicrobial regimens and 30-day mortality were assessed with Cox proportional hazards models, adjusting for baseline differences in patient characteristics, illness severity, and processes of care. Comparisons were made with patients treated with a non-pseudomonal third-generation cephalosporin alone (the reference group). RESULTS Initial treatment with a second-generation cephalosporin plus macrolide (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52-0.96), a non-pseudomonal third-generation cephalosporin plus macrolide (HR, 0.74; 95% CI, 0.60-0.92), or a fluoroquinolone alone (HR, 0.64; 95% CI, 0.43-0.94) was independently associated with lower 30-day mortality. Adjusted mortality among patients initially treated with these 3 regimens became significantly lower than that in the reference group beginning 2, 3, and 7 days, respectively, after hospital admission. Use of a beta-lactam/beta-lactamase inhibitor plus macrolide (HR, 1.77; 95% CI, 1.28-2.46) and an aminoglycoside plus another agent (HR, 1.21; 95% CI, 1.02-1.43) were associated with an increased 30-day mortality. CONCLUSIONS In this study of primarily community-dwelling elderly patients hospitalized with pneumonia, 3 initial empiric antimicrobial regimens were independently associated with a lower 30-day mortality. The more widespread use of these antimicrobial regimens is likely to improve the medical outcomes for elderly patients with pneumonia.
The presence of the TAR RNA structure alters the programmed -1 ribosomal frameshift efficiency of the human immunodeficiency virus type 1 (HIV-1) by modifying the rate of translation initiation

HIV-1 uses a programmed -1 ribosomal frameshift to synthesize the precursor of its enzymes, Gag-Pol. The frameshift efficiency that is critical for the virus replication, is controlled by an interaction between the ribosome and a specific structure on the viral mRNA, the frameshift stimulatory signal. The rate of cap-dependent translation initiation is known to be altered by the TAR RNA structure, present at the 5′ and 3′ end of all HIV-1 mRNAs. Depending upon its concentration, TAR activates or inhibits the double-stranded RNA-dependent protein kinase (PKR). We investigated here whether changes in translation initiation caused by TAR affect HIV-1 frameshift efficiency. CD4+ T cells and 293T cells were transfected with a dual-luciferase construct where the firefly luciferase expression depends upon the HIV-1 frameshift. Translation initiation was altered by adding TAR in cis or trans of the reporter mRNA. We show that HIV-1 frameshift efficiency correlates negatively with changes in the rate of translation initiation caused by TAR and mediated by PKR. A model is presented where changes in the rate of initiation affect the probability of frameshifting by altering the distance between elongating ribosomes on the mRNA, which influences the frequency of encounter between these ribosomes and the frameshift stimulatory signal.
We are deeply appreciative to Jeremy Stein for very insightful comments. We also thank Bengt Holmstrom,

Classic speculative bubbles are loud – price is high and so are price volatility and share turnover. The credit bubble of 2003-2007 is quiet – price is high but price volatility and share turnover are low. We develop a model, based on investor disagreement and short-sales constraints, that explains why credit bubbles are quieter than equity ones. Since debt up-side payoffs are bounded, debt is less sensitive to disagreement about asset value than equity and hence has a smaller resale option and lower price volatility and turnover. While optimism makes both debt and equity bubbles larger, it makes debt mispricings quiet but leaves the loudness of equity mispricings unchanged. Our theory suggests a taxonomy of bubbles. ∗Hong acknowledges support from the National Science Foundation through grant SES-0850404. We are deeply appreciative to Jeremy Stein for very insightful comments. We also thank Bengt Holmstrom, Sébastien Pouget, Eric Silvergold, Itay Goldstein, Alp Simsek and seminar participants at the NBER Monetary Economics Program, NBER Asset Pricing Program, Federal Reserve Board, Princeton University, MIT Sloan School of Management, Bendheim Center for Finance 10th anniversary conference, the 40th anniversary conference of Micro-Foundations for Macroeconomics at Columbia University, Casa das Garças in Rio De Janeiro, Australasian Banking and Finance Conference, Society for Financial Management Conference at National Taiwan University, the Brazilian Society for Finance, the Behavioral Finance Conference at Beijing University, for many helpful comments. This paper was previously circulated under the title ”A Taxonomy of Bubbles”. †Princeton University and NBER (e-mail: hhong@princeton.edu) ‡Princeton University (e-mail: dsraer@princeton.edu)
Multipotentiality, homing properties, and pyramidal neurogenesis of CNS‐derived LeX(ssea‐1)+/CXCR4+ stem cells

Achieving efficient distribution of neural stem cells throughout the central nervous system (CNS) and robust generation of specific neurons is a major challenge for the development of cell‐mediated therapy for neurodegenerative diseases. We isolated a primitive neural stem cell subset, double positive for LeX(Le) and CXCR4(CX) antigens that possesses CNS homing potential and extensive neuronal repopulating capacity. Le+CX+ cells are multipotential and can generate neurons as well as myogenic and endothelial cells. In vivo Le+CX+ cells displayed widespread incorporation and differentiated into cortical and hippocampal pyramidal neurons. Since intravenous delivery could be a less invasive route of transplantation, we investigated whether Le+CX+ cells could migrate across endothelial monolayers. Intracerebral coadministration of SDF enabled migration of intravenously injected Le+CX+ cells into the CNS and a small, yet significant, number of donor cells differentiated into neurons. The isolation of a specific neural stem cell population could offer major advantages to neuronal replacement strategies.
Perisaccadic Updating of Visual Representations and Attentional States: Linking Behavior and Neurophysiology

During natural vision, saccadic eye movements lead to frequent retinal image changes that result in different neuronal subpopulations representing the same visual feature across fixations. Despite these potentially disruptive changes to the neural representation, our visual percept is remarkably stable. Visual receptive field remapping, characterized as an anticipatory shift in the position of a neuron’s spatial receptive field immediately before saccades, has been proposed as one possible neural substrate for visual stability. Many of the specific properties of remapping, e.g., the exact direction of remapping relative to the saccade vector and the precise mechanisms by which remapping could instantiate stability, remain a matter of debate. Recent studies have also shown that visual attention, like perception itself, can be sustained across saccades, suggesting that the attentional control system can also compensate for eye movements. Classical remapping could have an attentional component, or there could be a distinct attentional analog of visual remapping. At this time we do not yet fully understand how the stability of attentional representations relates to perisaccadic receptive field shifts. In this review, we develop a vocabulary for discussing perisaccadic shifts in receptive field location and perisaccadic shifts of attentional focus, review and synthesize behavioral and neurophysiological studies of perisaccadic perception and perisaccadic attention, and identify open questions that remain to be experimentally addressed.
Predicting Tractor Diesel Fuel Consumption

General relationships capable of predicting tractor diesel fuel consumption are very useful for budget and management purposes but may not have the ability to compare fuel consumption for several potential engine configurations, such as turbocharging and air densifica-tion components. The objective of this factsheet is to examine several methods that use field measurements and Nebraska Tractor Test Laboratory results to estimate fuel consumption. Using these equations, farmers can estimate and compare the fuel savings for different operating and loading conditions.
2 8 Ju n 20 04 Detecting nonlinear corrosion by electrostatic measurements ∗

where Γ1 and Γ2 are two open, disjoint portions of ∂Ω and ΓD = ∂Ω \ (Γ1∪Γ2) and f is a Lipschitz function such that f(0) = 0. Such a problem with a specific choice of the profile of f , has been introduced and discussed in recent years by M.Vogelius and others for the modeling of the electrochemical phenomenon of surface corrosion in metals [7],[13],[20]. In the above boundary value problem, Ω represents the metal specimen, Γ1 represents the corroded part of the boundary, which is not accessible to direct inspection, Γ2 is the portion of the boundary which is accessible to measurements and ΓD is the remaining part of ∂Ω which is assumed to be grounded. The inverse problem thus consists in the determination of f when one pair of Cauchy data u|Γ2 , ∂u ∂ν |Γ2 is known for one non-trivial solution u to (1.1). It must be noted that the models of nonlinearity which have been discussed in [13],[20] are of the form
A collective sigh of relief: Local reactions to the establishment of new asylum centers in Norway

This article investigates a mood change in local communities where new asylum seeker facilities were established in the wake of the “refugee crisis” in 2015. Whereas opinions in flux are often studied using quantitative data, this analysis takes advantage of in-depth qualitative interviews with inhabitants in selected Norwegian local communities after new temporary asylum reception centers were established. Qualitative data collected at this particular time provide the opportunity to gain insight into social processes occurring in the wake of a sudden influx of immigrants. A key feature of the material is statements reflecting fear or nervous anticipation in relation to the period before the newcomers arrived, followed by descriptions of diminishing concern afterwards. Several studies have engaged with the issue of changes in public mood during this particular period, but few have analyzed changes at the local level. The study concludes that while the backdrop of impactful events that led to shifts in public mood at the national and regional levels played a role in informants’ imagined encounters with the newcomers, experiencing the presence of the newcomers resulted in a subtle mood change of increased acceptance.
Frontiers in Computational Neuroscience Computational Neuroscience

Neurons in PFC exhibit robust object-specific sustained activities during the delay periods of visual WM tasks like DMS or DNMS (Miller et al., 1996). However the informational content of WM-related activities in PFC is still unclear (Romanski, 2007). Inferotemporal (IT) neurons have been shown to encode object-specific information (Nakamura et al., 1994) as they are located at the end of the ventral visual pathway (Ungerleider and Mishkin, 1982). They have been shown to be critical for visual WM (Fuster et al., 1981; Petrides, 2000) and also exhibit sustained activation during the delay period, even if their responses can be attenuated or cancelled by intervening distractors (Miller et al., 1993), what can be partly explained by feedback cortico-cortical connections originating from PFC (Fuster et al., 1985; Webster et al., 1994). The medial temporal lobe (MTL, composed of perirhinal, PRh; entorhinal, ERh and parahippocampal, PH cortices) also plays an important also not essential role in visual WM. Compared to IT, a greater proportion of neurons in PRh and ERh exhibit sustained activation during the delay period (Nakamura and Kubota, 1995) and are robust to distractors (Suzuki et al., 1997). They are especially crucial when visual objects are novel and complex (Ranganath and D'Esposito, 2005). Particularly, PRh cells are more strongly involved in visual recognition when it requires visual WM processes (Lehky and Tanaka, 2007). They are reciprocally connected with IT neurons and can provide them with information about novelty or category membership since they can rapidly encode
Better Movers and Thinkers ( BMT ) : An Evaluation of How a Novel 1 Approach to Teaching Physical Education can Impact Children ’ s Physical 2 Activity , Coordination and Cognition

24 This study aimed to identify what impact a novel approach to teaching Physical Education (PE) 25 had on children’s physical activity, coordination and cognition compared to current provision. 26 150 children were recruited from 6 primary schools in Scotland. Outcome measures were the 27 “Cognitive Assessment System (CAS,” (Naglieri, 1997), the “Physical Activity Habits 28 Questionnaire for Children (PAQ-C),” (Kowalski, 2004) and fundamental locomotor skills 29 (crawling, creeping, marching and skipping). Pre-, postand 6-month follow-up testing was 30 conducted and data analysed comparing a control and an intervention group. Each group 31 received 2 hours of PE each week during the 16-week intervention. Current provision in PE 32 was delivered in the control group and a Better Movers and Thinkers (BMT) approach to PE 33 delivered in the intervention group. Significant effects of intervention relative to the control 34 group were identified in cognition (p = <.001, d = 0.76) and coordination (p = <.001, d = 0.97). 35 No significant effects of intervention were identified for physical activity (p = > .200, d = 0.24). 36 The improvement in the outcome measures remained at the 6-month follow-up testing. The 37 present study has identified cognitive and coordination improvements as a result of a novel PE 38 intervention with benefits maintained 6 months later. This supports the need for modification 39 in current PE provision to optimise the potential for learning across the curriculum. 40
The Limits of Gendered Leadership: The Public Policy Implications of Female Leadership on Women’s IssuesThe Limits of Gendered Issues

Although we know that female representatives are more likely to sponsor women’s issue bills, it is unclear whether and how this type of gendered leadership influences the substance of legislation. We seek to address this question by exploring the potential policy ramifications of issue gendering based on female leadership of women’s issues. Specifically, we ask what impact the percentage of females sponsoring a bill, and the percentage of bill sponsors that are female, have on the content of women’s issue laws. We choose as our test case a contemporary public policy issue that has become gendered and in which states can choose to invest abundantly or not at all: the issue of human trafficking. Based on an analysis of human trafficking legislation in every state from 2003 to 2008, we designed a unique dataset that determines how much a state has invested in the issue of human trafficking. This quantitative approach, coupled with qualitative data obtained through a myriad of interviews, yields findings that suggest states are most likely to invest in ‘women’s issue’ areas when both female and male legislators take a significant leadership role. These results call into question whether the link between descriptive and substantive representation - which has been assumed to be unequivocally advantageous - is indeed beneficial for passing truly substantive legislation for women.
Communications in Mathematical Physics On Strong Superadditivity of the Entanglement of Formation

We employ a basic formalism from convex analysis to show a simple relation between the entanglement of formation EF and the conjugate function E∗ of the entanglement function E(ρ) = S(TrAρ). We then consider the conjectured strong superadditivity of the entanglement of formation EF (ρ) ≥ EF (ρI ) + EF (ρII ), where ρI and ρII are the reductions of ρ to the different Hilbert space copies, and prove that it is equivalent with subadditivity ofE∗. Furthermore, we show that strong superadditivity would follow from multiplicativity of the maximal channel output purity for quantum filtering operations, when purity is measured by Schatten p-norms for p tending to 1.