Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of single voltage‐gated Na+ and Ca2+ channels in apical dendrites of rat CA1 pyramidal neurons.

1. We have used dendrite‐attached patch‐clamp techniques to record single Na+ and Ca2+ channel activity from the apical dendrites (up to 350 microns away from soma) of CA1 pyramidal neurons in rat hippocampal slices (ages: 2‐8 weeks). 2. Na+ channels were found in every patch examined (range: 2 to > 20 channels per patch). Channel openings, which had a slope conductance of 15 +/‐ 0.3 pS (mean +/‐ S.E.M.), began with test commands to around ‐50 mV and consisted of both early transient channel activity and also later occurring prolonged openings of 5‐15 ms. All Na+ channel activity was suppressed by inclusion of TTX (1 microM) in the recording pipette. 3. Ca2+ channel activity was recorded in about 80% of the patches examined (range: 1 to > 10 channels per patch). Several types of channel behaviour were observed in these patches. Single channel recordings in 110 mM BaCl2, revealed an approximately 10 pS channel of small unitary current amplitude (‐0.5 pA at ‐20 mV). These channels began activating at relatively hyperpolarized potentials (‐50 mV) and ensemble averages of this low voltage‐activated (LVA) channel activity showed rapid inactivation. 4. A somewhat heterogeneous population of high voltage‐activated, moderate conductance (HVAm; approximately 17 pS), Ca2+ channel activity was also encountered. These channels exhibited a relatively large unitary amplitude (‐0.8 pA at 0 mV) and ensemble averages demonstrated moderate inactivation. The HVAm population of channels could be tentatively subdivided into two separate groups based upon mean channel open times. 5. Less frequently, HVA, large conductance (27 pS) Ca2+ channel activity (HVA1) was also observed. This large unitary amplitude (‐1.5 pA at 0 mV) channel activity began with steps to approximately 0 mV and ensemble averages did not show any time‐dependent inactivation. The dihydropyridine Ca2+ channel agonist Bay K 8644 (0.5 or 1 microM) was found to characteristically prolong these channel openings. 6. omega‐Conotoxin MVIIC (10 microM), did not significantly reduce the amount of channel activity recorded from the LVA, HVAm or HVA1 channel types in dendritic patches. In patches from somata, omega‐conotoxin MVIIC was effective in eliminating a significant amount of HVAm Ca2+ channel activity. Inclusion of 50 or 100 microM NiCl2 to the recording solution significantly reduced the amount of channel activity recorded from LVA and HVAm channel types in dendritic patches. A subpopulation of HVAm channels was, however, found to be Ni2+ insensitive. Dendritic HVA, channel activity was unaffected by these low concentrations of Ni2+. (ABSTRACT TRUNCATED AT 400 WORDS)
Endogenous Network Formation in Congress

This paper presents and structurally estimates a model of endogenous network formation and legislative activity of career-motivated politicians. Employing data on socialization and legislative effort of members of the 105th-110th U.S. Congresses, our model reconciles a set of empirical regularities, including: recent trends in Congressional productivity; the complementarity of socialization processes and legislative activities in the House of Representatives; substantial heterogeneity across legislators in terms of effort and success rate in passing specific legislation. We avoid taking the social structure of Congress as exogenously given and instead embed it in a model of endogenous network formation useful for developing relevant counterfactuals, including some pertinent to the congressional emergency response to the 2008-09 financial crisis. Our counterfactual analysis further demonstrates how to empirically identify the specific equilibrium at play within each Congress among the multiple equilibria typically present in this class of games.
Herpes Simplex Virus 1 ICP0 Phosphorylation Site Mutants Are Attenuated for Viral Replication and Impaired for Explant-Induced Reactivation

ABSTRACT In cell culture experiments, phosphorylation appears to be a critical regulator of the herpes simplex virus 1 (HSV-1) immediate-early (IE) protein, ICP0, which is an E3 ubiquitin ligase that transactivates viral gene expression. Three major regions of phosphorylation in ICP0 (amino acids 224 to 232, 365 to 371, and 508 to 518) have been identified, and mutant viruses that block phosphorylation sites within each region (termed Phos 1, 2, and 3, respectively) have been constructed. Previous studies indicated that replication of Phos 1 is significantly reduced compared to that of wild-type virus in cell culture (C. Boutell, et al., J. Virol. 82:10647–10656, 2008). To determine the effects these phosphorylation site mutations have on the viral life cycle in vivo, mice were ocularly infected with wild-type HSV-1, the Phos mutants, or their marker rescue counterparts. Subsequently, viral replication, establishment of latency, and viral explant-induced reactivation of these viruses were examined. Relative to wild-type virus, Phos 1 eye titers were reduced as much as 7- and 18-fold on days 1 and 5 postinfection, respectively. Phos 2 eye titers showed a decrease of 6-fold on day 1 postinfection. Titers of Phos 1 and 2 trigeminal ganglia were reduced as much as 16- and 20-fold, respectively, on day 5 postinfection. Additionally, the reactivation efficiencies of Phos 1 and 2 were impaired relative to wild-type HSV-1, although both viruses established wild-type levels of latency in vivo. The acute replication, latency, and reactivation phenotypes of Phos 3 were similar to those of wild-type HSV-1. We conclude from these studies that phosphorylation is likely a key modulator of ICP0's biological activities in a mouse ocular model of HSV-1 infection.
Beneficial effects of androgen-primed chemotherapy in the Dunning R3327 G model of prostatic cancer.

The objective of this study was to test the hypothesis that androgen administration prior to chemotherapy (androgen priming) may potentiate tumor cytotoxicity in hormone-responsive prostate cancer. Accordingly, six groups of Copenhagen rats bearing small (i.e., 40-mm3 median volume) Dunning R3327 G tumors were left untreated or received castration, chemotherapy, or a combination of the two, with or without androgen priming. Groups without priming included: intact untreated, castrate alone, intact plus chemotherapy, and castrate plus chemotherapy (cyclophosphamide, 30 mg/kg/day, for 2 days, with repeat cycle in 24 days) (Cx). To specifically evaluate the effect of androgen priming on Cx cytotoxicity, two additional castrate groups were studied. One received testosterone propionate (4 mg/kg/day) for 2 days prior to Cx and the other after Cx. Treatment effect was evaluated by quantitating tumor volume as well as animal survival to an ethically allowable, maximal tumor burden. As expected, castration and Cx produced a retardation of tumor growth and prolongation of survival when compared to untreated animals. The addition of androgen priming prior to but not after Cx enhanced the degree of tumor suppression. Specifically, 26 days after the second Cx cycle, all androgen-primed tumors had regressed; 70% of tumors had disappeared and those remaining were barely palpable. At this same time point, tumors in all the other groups were actively growing and had volumes greater than initial values (P less than 0.01). Although tumor regrowth occurred, median survival for the androgen-primed group was significantly prolonged, to 186 days versus 39 days (P less than 0.01) for untreated animals and 153 days for the non-primed castrate plus Cx animals (P less than 0.01). These data suggested that androgen priming potentiates the effects of Cx in castrate animals bearing R3327 G tumors.
The H3-H4 N-Terminal Tail Domains Are the Primary Mediators of Transcription Factor IIIA Access to 5S DNA within a Nucleosome

ABSTRACT Reconstitution of a DNA fragment containing a Xenopus borealis somatic type 5S rRNA gene into a nucleosome greatly restricts the binding of transcription factor IIIA (TFIIIA) to its cognate DNA sequence within the internal promoter of the gene. Removal of all core histone tail domains by limited trypsin proteolysis or acetylation of the core histone tails significantly relieves this inhibition and allows TFIIIA to exhibit high-affinity binding to nucleosomal DNA. Since only a single tail or a subset of tails may be primarily responsible for this effect, we determined whether removal of the individual tail domains of the H2A-H2B dimer or the H3-H4 tetramer affects TFIIIA binding to its cognate DNA site within the 5S nucleosome in vitro. The results show that the tail domains of H3 and H4, but not those of H2A and/or H2B, directly modulate the ability of TFIIIA to bind nucleosomal DNA. In vitro transcription assays carried out with nucleosomal templates lacking individual tail domains show that transcription efficiency parallels the binding of TFIIIA. In addition, we show that the stoichiometry of core histones within the 5S DNA-core histone-TFIIIA triple complex is not changed upon TFIIIA association. Thus, TFIIIA binding occurs by displacement of H2A-H2B–DNA contacts but without complete loss of the dimer from the nucleoprotein complex. These data, coupled with previous reports (M. Vettese-Dadey, P. A. Grant, T. R. Hebbes, C. Crane-Robinson, C. D. Allis, and J. L. Workman, EMBO J. 15:2508–2518, 1996; L. Howe, T. A. Ranalli, C. D. Allis, and J. Ausio, J. Biol. Chem. 273:20693–20696, 1998), suggest that the H3/H4 tails are the primary arbiters of transcription factor access to intranucleosomal DNA.
Population-Based Screening for Rare Mutations: High-Throughput DNA Extraction and Molecular Amplification from Guthrie Cards

To determine the population-based frequency of a rare mutation (the 121ins2 mutation in the surfactant protein B gene), we developed high-throughput techniques to extract reliably and rapidly amplifiable DNA from Guthrie cards. Using a 3-mm punch from each of 10,044 Guthrie cards obtained from the Missouri Department of Health, we extracted DNA with deionized water by heating in the presence of 2% Chelex in a 96-well format. Average yield of DNA from each punch was 52.6 ± 21 μg. Using 36mer primers and a 10-μL reaction volume, we amplified a 354-bp fragment of the surfactant protein B gene that contained the mutation and identified the mutation by its susceptibility to restriction enzyme digestion with Sfu I. The procedure required 5 h per 96 samples but only 2 h of technician time. The amplification rate on the first attempt was 99.2%. Based on detection of eight individuals heterozygous for the mutation (confirmed by direct sequencing), we estimate the allele frequency to be 0.8/1000 individuals, an estimate not significantly different from previous estimates based on independent methods. High-throughput DNA extraction and amplification will permit establishment of DNA banks as well as efficient estimation of population-based genotype frequency for both rare and common genetic disorders.
Effect of Ageing on the Ownership of Durable Goods

I analyse how ageing affects the demand for non-housing durable goods. Based on the English Longitudinal Study of Ageing, individual characteristics, cohort and time effects can explain most of the age variation in the ownership and purchase of durable goods. A life-cycle model is derived to capture the complex relation between ageing and the demand for non-housing durable goods. Decreasing survival probability, deteriorating health and changing preferences are jointly reflected in the age gradient of demand. Simulations indicate that higher chances of survival increase the ownership ratio of the durable items.
Receiver Design for Molecular Communication

In the Molecular Communication (MC), molecules are utilized to encode, transmit, and receive information. Transmission of the information is achieved by means of diffusion of molecules and the information is recovered based on the molecule concentration variations at the receiver location. The MC is very prone to intersymbol interference (ISI) due to residual molecules emitted previously. Furthermore, the stochastic nature of the molecule movements adds noise to the MC. For the first time, we propose four methods for a receiver in the MC to recover the transmitted information distorted by both ISI and noise. We introduce sequence detection methods based on maximum a posteriori (MAP) and maximum likelihood (ML) criterions, a linear equalizer based on minimum mean-square error (MMSE) criterion, and a decision-feedback equalizer (DFE) which is a nonlinear equalizer. We present a channel estimator to estimate time varying MC channel at the receiver. The performances of the proposed methods based on bit error rates are evaluated. The sequence detection methods reveal the best performance at the expense of computational complexity. However, the MMSE equalizer has the lowest performance with the lowest computational complexity. The results show that using these methods significantly increases the information transmission rate in the MC.
Legal Empowerment of the Poor through Property Rights Reform: Tensions and Trade-offs of Land Registration and Titling in Sub-Saharan Africa

Abstract Land registration and titling in Africa is often advocated as a pro-poor legal empowerment strategy. Advocates have put forth different visions of the substantive goals this is to achieve. Some see registration and titling as a way to protect smallholders’ rights of access to land. Others frame land registration as part of community-protection or ethno-justice agendas. Still others see legal empowerment in the market-enhancing commodification of property rights. This paper contrasts these different visions, showing that each entails tensions and trade-offs. The analysis helps explain why land law reforms aiming at legal empowerment may be controversial or divisive in African countries.
RC/BTB2 is essential for formation of primary cilia in mammalian cells

RC/BTB2 is a binding partner of sperm associated antigen 16S (SPAG16S), which is a regulator of spermiogenesis in mice, a process during which sperm flagella are formed. The expression of Rc/btb2 is also regulated by multicilin, a protein that controls ciliogenesis. Given that mouse Rc/btb2 mRNA is not only expressed in tissues bearing motile cilia, but also in tissues without motile cilia, we investigated whether RC/BTB2 plays a role in the general process of ciliogenesis by studying two cell lines that have primary cilia, NIH3T3, and IMCD3. We discovered that the subcellular localization of RC/BTB2 in the NIH3T3 and IMCD3 cells encompasses the pathway for ciliogenesis. RC/BTB2 was found in the Golgi bodies and centrosomes, two key structures essential for normal ciliogenesis. Knockdown of Rc/btb2 gene expression in these cell lines disrupted ciliogenesis. The percentage of cells with primary cilia was significantly reduced in stable cell lines transduced with specific Rc/btb2 shRNA viruses as compared to the control cells. When cilia were formed in the knockdown cells, they were significantly shorter than those in the control cells. Knockdown of Rc/btb2 expression did not affect cell proliferation and the cell cycle. Exogenous expression of RC/BTB2 in these stable knockdown cells restored ciliogenesis. These findings suggest that RC/BTB2 is a necessary component of the process of formation of primary cilia in somatic cells, perhaps through the transportation of cargos from Golgi bodies to centrosomes for cilia assembling. © 2015 Wiley Periodicals, Inc.
Cardiovascular risk factors and incident acute renal failure in older adults: the cardiovascular health study.

BACKGROUND AND OBJECTIVES Although the elderly are at increased risk for acute renal failure, few prospective studies have identified risk factors for acute renal failure in the elderly. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The associations of cardiovascular disease risk factors, subclinical cardiovascular disease, and clinical coronary heart disease with the risk for development of acute renal failure were examined in older adults in the Cardiovascular Health Study, a prospective cohort study of community-dwelling older adults. Incident hospitalized cases of acute renal failure were identified through hospital discharge International Classification of Diseases, Ninth Revision codes and confirmed through physician diagnoses of acute renal failure in discharge summaries. RESULTS Acute renal failure developed in 225 (3.9%) of the 5731 patients during a median follow-up period of 10.2 yr. In multivariate analyses, diabetes, current smoking, hypertension, C-reactive protein, and fibrinogen were associated with acute renal failure. Prevalent coronary heart disease was associated with incident acute renal failure, and among patients without prevalent coronary heart disease, subclinical vascular disease measures were also associated with acute renal failure: Low ankle-arm index (< or =0.9), common carotid intima-media thickness, and internal carotid intima-media thickness. CONCLUSIONS In this large, population-based, prospective cohort study, cardiovascular risk factors and both subclinical and clinical vascular disease were associated with incident acute renal failure in the elderly.
Partial remission phase of diabetes in children younger than age 10 years

There is renewed interest in the phase of partial remission in recently diagnosed diabetes because of the potential for pharmacological and immune intervention to preserve β cell function. 95 children younger than 10 years were investigated to assess the influence of age, sex, diabetic ketoacidosis (DKA), admission at diagnosis, and ethnicity on the frequency of remission and insulin requirements during the first two years after diagnosis. Partial remission was defined as a requirement of insulin < 0.5 U/kg body weight/day. There was partial remission in 41 patients, with no differences for children aged 2–4 years and those aged 5–9 years. None of the five children aged < 2 years remitted. Forty five of 95 children were admitted to hospital at diagnosis, of whom 26 of 45 had DKA (blood pH < 7.25). In this number of children we were unable to show a statistical difference in the rate of remission with respect to DKA, admission to hospital at diagnosis, sex, or South Asian ethnic background. There were no differences in insulin requirements between the different groups by the end of two years and at that time seven of the children required insulin < 0.5 U/kg/day. The results suggest that even in preschool children there is potential for attempting to preserve β cell function.
Listeria monocytogenes as a vector for tumor-associated antigens for cancer immunotherapy

As a facultative intracellular bacterium, Listeria monocytogenes has adapted to live within the cytosol of the host cell. It is actively taken up by antigen-presenting cells through phagocytosis, and as Listeria survive within these cells, it is an ideal vector for the delivery of antigens to be processed and presented through both the class I and II antigen-processing pathways. Once phagocytosed, Listeria produces virulence factors within the phagolysosome of the host cell, which allows it to break out of this organelle and live in the host cytosol. It is possible that these virulence factors can enhance the immunogenicity of tumor-associated antigens, which are poorly immunogenic. Recent progress in the development of this bacterium as a vaccine vector for tumor-associated antigens is discussed in the context of bacterial vectors in general. In several mouse models, Listeria -based vaccines have been demonstrated to be an effective method of influencing tumor growth and eliciting potent antitumor immune responses. Safety issues and the transition of Listeria into human clinical trials will also be discussed in this review.
Fibroblast Growth Factor 21 Promotes C2C12 Cells Myogenic Differentiation by Enhancing Cell Cycle Exit

Fibroblast growth factor 21 (FGF21), a secretion protein, functions as a pivotal regulator of energy metabolism and is being considered as a therapeutic candidate in metabolic syndromes. However, the roles of FGF21 in myogenic differentiation and cell cycle remain obscure. In this study, we investigated the function of FGF21 in myogenesis and cell cycle exit using C2C12 cell line. Our data showed that the expression of myogenic genes as well as cell cycle exit genes was increased after FGF21 overexpression, and FGF21 overexpression induces cell cycle arrest. Moreover, cell cycle genes were decreased in FGF21 overexpression cells while they were increased in FGF21 knockdown cells. Further, FGF21/P53/p21/Cyclin-CDK has been suggested as the key pathway for cell cycle exit mediated by FGF21 in C2C12 cells. Also, we deduce that FGF21 promotes the initiation of myogenic differentiation mainly through enhancing cell cycle exit of C2C12 cells. Taken together, our results demonstrated that FGF21 promotes cell cycle exit and enhances myogenic differentiation of C2C12 cells. This study provided new evidence that FGF21 promotes myogenic differentiation, which could be useful for better understanding the roles of FGF21 in myogenesis.
Central Bank Foreign Exchange Market Intervention and Option Contract Specification: The Case of Colombia

This paper aims to identify appropriate option contract specifications for effective central bank exchange market intervention. Option contract specifications determine the impact of options on the underlying asset or currency, and hence their actual effect on asset price or currency volatility and are therefore key to determining the effectiveness of option-based intervention. The paper reviews the experience of the systematic option-based foreign exchange market intervention of the Central Bank of Colombia and finds that its contract has only been moderately successful at abating exchange rate volatility, which is attributed here to sub-optimal contract specifications.
Gabexate Mesilate, a Synthetic Protease Inhibitor, Inhibits Lipopolysaccharide-Induced Tumor Necrosis Factor-α Production by Inhibiting Activation of Both Nuclear Factor-κB and Activator Protein-1 in Human Monocytes

Gabexate mesilate, a synthetic protease inhibitor, was shown to be effective in treating patients with sepsis-associated disseminated intravascular coagulation in which tumor necrosis factor-α (TNF-α) plays a critical role. We demonstrated that gabexate mesilate reduced lipopolysaccharide (LPS)-induced tissue injury by inhibiting TNF-α production in rats. In the present study, we analyzed the mechanism(s) by which gabexate mesilate inhibits LPS-induced TNF-α production in human monocytes in vitro. Gabexate mesilate inhibited the production of TNF-α in monocytes stimulated with LPS. Gabexate mesilate inhibited both the binding of nuclear factor-κB (NF-κB) to target sites and the degradation of inhibitory κBα. Gabexate mesilate also inhibited both the binding of activator protein-1 (AP-1) to target sites and the activation of mitogen-activated protein kinase pathways. These observations strongly suggest that gabexate mesilate inhibited LPS-induced TNF-α production in human monocytes by inhibiting activation of both NF-κB and AP-1. Inhibition of TNF-α production by gabexate mesilate might explain at least partly its therapeutic effects in animals given LPS and those in patients with sepsis.
Evaluation of Delaware Stars for Early Success: Year 1 Report. Research Report.

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