Miracle-dz/UniFAR-FTUs huggingface dataset:
Francisella novicida inhibits spontaneous apoptosis and extends human neutrophil lifespan

Francisella novicida is a Gram‐negative bacterium that is closely related to the highly virulent facultative intracellular pathogen, Francisella tularensis. Data published by us and others demonstrate that F. tularensis virulence correlates directly with its ability to impair constitutive apoptosis and extend human neutrophil lifespan. In contrast, F. novicida is attenuated in humans, and the mechanisms that account for this are incompletely defined. Our published data demonstrate that F. novicida binds natural IgG that is present in normal human serum, which in turn, elicits NADPH oxidase activation that does not occur in response to F. tularensis. As it is established that phagocytosis and oxidant production markedly accelerate neutrophil death, we predicted that F. novicida may influence the neutrophil lifespan in an opsonin‐dependent manner. To test this hypothesis, we quantified bacterial uptake, phosphatidylserine (PS) externalization, and changes in nuclear morphology, as well as the kinetics of procaspase‐3, ‐8, and ‐9 processing and activation. To our surprise, we discovered that F. novicida not only failed to accelerate neutrophil death but also diminished and delayed apoptosis in a dose‐dependent, but opsonin‐independent, manner. In keeping with this, studies of conditioned media (CM) showed that neutrophil longevity could be uncoupled from phagocytosis and that F. novicida stimulated neutrophil secretion of CXCL8. Taken together, the results of this study reveal shared and unique aspects of the mechanisms used by Francisella species to manipulate neutrophil lifespan and as such, advance understanding of cell death regulation during infection.
Proteomic and Virus-induced Gene Silencing (VIGS) Analyses Reveal That Gossypol, Brassinosteroids, and Jasmonic acid Contribute to the Resistance of Cotton to Verticillium dahliae *

Verticillium wilt causes massive annual losses of cotton yield, but the mechanism of cotton resistance to Verticillium dahliae is complex and poorly understood. In this study, a comparative proteomic analysis was performed in resistant cotton (Gossypium barbadense cv7124) on infection with V. dahliae. A total of 188 differentially expressed proteins were identified by mass spectrometry (MALDI-TOF/TOF) analysis and could be classified into 17 biological processes based on Gene Ontology annotation. Most of these proteins were implicated in stimulus response, cellular processes and metabolic processes. Based on the proteomic analysis, several genes involved in secondary metabolism, reactive oxygen burst and phytohormone signaling pathways were identified for further physiological and molecular analysis. The roles of the corresponding genes were further characterized by employing virus-induced gene silencing (VIGS). Based on the results, we suggest that the production of gossypol is sufficient to affect the cotton resistance to V. dahliae. Silencing of GbCAD1, a key enzyme involving in gossypol biosynthesis, compromised cotton resistance to V. dahliae. Reactive oxygen species and salicylic acid signaling may be also implicated as regulators in cotton responsive to V. dahliae according to the analysis of GbSSI2, an important regulator in the crosstalk between salicylic acid and jasmonic acid signal pathways. Moreover, brassinosteroids and jasmonic acid signaling may play essential roles in the cotton disease resistance to V. dahliae. The brassinosteroids signaling was activated in cotton on inoculation with V. dahliae and the disease resistance of cotton was enhanced after exogenous application of brassinolide. Meanwhile, jasmonic acid signaling was also activated in cotton after inoculation with V. dahliae and brassinolide application. These data provide highlights in the molecular basis of cotton resistance to V. dahliae.
An extended Shine–Dalgarno sequence in mRNA functionally bypasses a vital defect in initiator tRNA

Significance Initiation, a regulatory step in mRNA translation is characterized by initiator tRNA (tRNAfMet) binding to 30S ribosome together with initiation factors (IFs) to form 30S pre-initiation complex (PIC). This step is followed by binding of 50S ribosome and release of IFs to form elongation competent 70S complex. tRNAfMet is special in possessing a vital feature of three consecutive G-C (3GC) base pairs in its anticodon stem. However, the role of this feature has remained unclear. We show that the 3GC base pairs facilitate tRNAfMet retention in the ribosome during the transitions that mark conversion of 30S PIC into 70S complex. Furthermore, we show that translation of mRNAs having an extended Shine–Dalgarno sequence bypasses the requirement of the 3GC pairs in tRNAfMet. Initiator tRNAs are special in their direct binding to the ribosomal P-site due to the hallmark occurrence of the three consecutive G-C base pairs (3GC pairs) in their anticodon stems. How the 3GC pairs function in this role, has remained unsolved. We show that mutations in either the mRNA or 16S rRNA leading to extended interaction between the Shine–Dalgarno (SD) and anti-SD sequences compensate for the vital need of the 3GC pairs in tRNAfMet for its function in Escherichia coli. In vivo, the 3GC mutant tRNAfMet occurred less abundantly in 70S ribosomes but normally on 30S subunits. However, the extended SD:anti-SD interaction increased its occurrence in 70S ribosomes. We propose that the 3GC pairs play a critical role in tRNAfMet retention in ribosome during the conformational changes that mark the transition of 30S preinitiation complex into elongation competent 70S complex. Furthermore, treating cells with kasugamycin, decreasing ribosome recycling factor (RRF) activity or increasing initiation factor 2 (IF2) levels enhanced initiation with the 3GC mutant tRNAfMet, suggesting that the 70S mode of initiation is less dependent on the 3GC pairs in tRNAfMet.
Strong FEM solution for the square coaxial line

In this paper the strong FEM formulation based on hierarchical basis functions of higher order and Galerkin method is proposed. This physically means that the boundary conditions-continuity of the electric potential V and of the normal component of vector D, on element boundaries are exactly satisfied. As a benchmark example, a coaxial transmission line of the square cross section is analyzed.
Chemotherapeutic Prevention of Complications Caused by Vaccinia Virus‐Vectored Immunogen a

Vaccinia virus strains and constructs differ greatly in the number of PFUs required to produce tail lesions in the vaccinia virus mouse model. The pathogenesis of lesion formation appeared to involve virus spread from an initial focus in specific cells surrounding hair follicles to other concentrated areas of the dermis and finally, at the time of lesion development, to the epidermis. Antivirals that suppressed tail lesions, to a greater or lesser degree, included ara A, ribavirin, rifampicin, adenosine N'-oxide, and selected analogues. Immunomodulators, including ampligen and recombinant interferon, suppressed lesions at very low doses. Spread of virus infection from the dermis to the epidermis was inhibited as determined by immunofluorescence. These studies in the tail lesion model have suggested drugs that could be tested further in primate models of vaccinia virus infection. In addition, these studies provide additional data on a model that may be a useful adjunct in safety testing of recombinant vaccinia virus vaccines.
Metastatic primitive neuroectodermal tumor of the ovary in pregnancy

Primitive neuroectodermal tumor (PNET) is a small round tumor belonging to the PNET/Ewing's sarcoma family. We hereby report a case of PNET of the ovary, which was detected at the second trimester of pregnancy. Chemotherapy was administered and a healthy baby was delivered by cesarean section. After the pregnancy, the mother was found to have metastatic disease. Chemotherapy was continued, but she died due to progressive disease 13 months after the initial diagnosis. In this case report, we discuss chemotherapy options during pregnancy and the importance of multidisciplinary approach to unusual presentations of rare tumors
Determination of Binding Thermodynamics

This unit serves as a starting point for exploring the thermodynamic properties of interactions between small molecules and DNA. It covers the determination of simple, apparent association/dissociation constants. The concentration of DNA‐bound ligand and free ligand are determined and a binding constant is extracted from these data. Data gathering and curve fitting are discussed.
Agriculture investment, output growth, and CO2 emissions relationship

ABSTRACT The purpose of this study is to examine the dynamic relationships between foreign investments in agriculture, domestic investments in agriculture, agricultural output, and greenhouse gases emissions from agriculture for a panel of countries over the period of 1990–2007. The panel cointegration and panel causality tests are applied in this study. The results show that there is a long-run causal relationship among all variables. The short-run dynamics suggest that there is a bidirectional causality relationship between agricultural output and greenhouse gases emissions from agriculture while there is no causal relationship between foreign investments in agriculture and domestic investments in agriculture as well as foreign investments in agriculture and greenhouse gases emissions from agriculture. It is also found that there is unidirectional short-run causal relationship from agricultural output to domestic investments in agriculture. The results provide some important implications for policy-makers.
Electroconvulsive seizure restores neurogenesis and hippocampus‐dependent fear memory after disruption by irradiation

Ongoing neurogenesis in the adult hippocampus is thought to play a role in learning and memory processes, and in response to antidepressant treatments. Low doses of irradiation (IRR) produce a significant long‐lasting inhibitory effect on hippocampal neurogenesis that correlates with long‐lasting behavioral deficits. Here we report that electroconvulsive seizure (ECS), which robustly increases adult neurogenesis in naïve animals, also reverses the disruption of neurogenesis produced by IRR exposure. Moreover, we find that vascular endothelial growth factor (VEGF) is an essential mediator of this effect. Expression of VEGF in the granule cell layer (GCL) of the hippocampus is decreased by IRR, and ECS administration reverses this deficit in VEGF. There is a corresponding alteration in the number of endothelial cells, which express VEGF, in the hippocampal GCL following IRR and ECS. We also find that blockade of VEGF signaling attenuates ECS‐induced proliferation, and VEGF infusion partially restores proliferation in irradiated animals. To examine the functional consequences of IRR and ECS on neurogenesis, hippocampus‐dependent contextual fear conditioning was assessed. We found that following disruption by IRR, ECS restores contextual learning to baseline levels at time points consistent with its effects on neurogenesis. These findings demonstrate that ECS, in part via induction of VEGF, can reverse long‐term neurogenesis deficits resulting from IRR, and that these effects have functional consequences on hippocampus‐dependent fear memory.
The Economics of Asset Management 1

This paper develops a contingent claims approach to valuing the fee flow generated by mutual funds. The method incorporates the key empirical characteristic of mutual funds, namely the relation between fund performance and fund inflows. Using this approach, we address a number of central issues in asset management such as the risk-taking incentives of mutual funds, the value of active management, and the optimal fund contract.
Pervasive compensatory adaptation in Escherichia coli

To investigate compensatory adaptation (CA), we used genotypes of Escherichia coli which were identical except for one or two deleterious mutations. We compared CA for (i) deleterious mutations with large versus small effects, (ii) genotypes carrying one versus two mutations, and (iii) pairs of deleterious mutations which interact in a multiplicative versus synergistic fashion. In all, we studied 14 different genotypes, plus a control strain which was not mutated. Most genotypes showed CA during 200 generations of experimental evolution, where we define CA as a fitness increase which is disproportionately large relative to that in evolving control lines, coupled with retention of the original deleterious mutation(s). We observed greater CA for mutations of large effect than for those of small effect, which can be explained by the greater benefit to recovery in severely handicapped genotypes given the dynamics of selection. The rates of CA were similar for double and single mutants whose initial fitnesses were approximately equal. CA was faster for synergistic than for multiplicative pairs, presumably because the marginal gain which results from CA for one of the component mutations is greater in that case. The most surprising result in our view, is that compensation should be so readily achieved in an organism which is haploid and has little genetic redundancy. This finding suggests a degree of versatility in the E. coli genome which demands further study from both genetic and physiological perspectives.
Establishing Benchmarks Across Groups

Pressures on colleges and universities have spawned numerous studies to improve our understanding of faculty and their worklives, including examinations of faculty satisfaction, morale, motivation and productivity, reward, and retention and turnover. In response to external pressures for improved accountability in higher education, institutional leaders seek to identify outcome measures and generate benchmarks that can be used to assess change over time. The purpose of this study is to propose a structural model of faculty worklife and to test its generalizability by examining possible differences in the model across three cross-sectional samples of probationary faculty at a major research university. Identified trends in faculty perceptions about their worklife over time can be used as benchmarks to aid institutions in retaining faculty by monitoring and improving aspects of their worklives.
Purification and activation of the double-stranded RNA-dependent eIF-2 kinase DAI

The double-stranded RNA (dsRNA)-dependent protein kinase DAI (also termed dsI and P1) possesses two kinase activities; one is an autophosphorylation activity, and the other phosphorylates initiation factor eIF-2. We purified the enzyme, in a latent form, to near homogeneity from interferon-treated human 293 cells. The purified enzyme consisted of a single polypeptide subunit of approximately 70,000 daltons, retained its dependence on dsRNA for activation, and was sensitive to inhibition by adenovirus VA RNAI. Autophosphorylation required a suitable concentration of dsRNA and was second order with respect to DAI concentration, which suggests an intermolecular mechanism in which one DAI molecule phosphorylates a neighboring molecule. Once autophosphorylated, the enzyme could phosphorylate eIF-2 but seemed unable to phosphorylate other DAI molecules, which implies a change in substrate specificity upon activation. VA RNAI blocked autophosphorylation and activation but permitted the activated enzyme to phosphorylate eIF-2. VA RNAI also blocked the binding of dsRNA to the enzyme. The data are consistent with a model in which activation requires the interaction of two molecules of DAI with dsRNA, followed by intermolecular autophosphorylation of the latent enzyme. VA RNAI would block activation by preventing the interaction between DAI and dsRNA.
Use of replication-competent retroviral vectors in an immunocompetent intracranial glioma model.

OBJECT The authors had previously reported on a replication-competent retrovirus (RCR) that has been demonstrated to be stable, capable of effective transduction, and able to prolong survival in an intracranial tumor model in nude mice. The purpose of this study was further investigation of this gene therapy option. METHODS The transduction efficiency of RCR in RG2, an immunocompetent intracranial tumor model, was tested in Fischer 344 rats. The immune response to the RCR vector was expressed by the quantification of CD4, CD8, and CD11/b in tumors. The pharmaceutical efficacy of the suicide gene CD in converting prodrug 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU) was measured using fluorine-19 nuclear magnetic resonance (19F-NMR) spectroscopy. Animal survival data were plotted on Kaplan-Meier survival curves. Finally, the biodistribution of RCR was determined using quantitative real-time polymerase chain reaction (RT-PCR) for the detection of retroviral env gene. There was no evidence of viral transduction in normal brain cells. Neither severe inflammation nor immunoreaction occurred after intracranial injection of RCR-green fluorescent protein compared with phosphate-buffered saline (PBS). The 19F-NMR spectroscopy studies demonstrated that RCR-CD was able to convert 5-FC to 5-FU effectively in vitro. The infection of RG2 brain tumors with RCR-CD and their subsequent treatment with 5-FC significantly prolonged survival compared with that in animals with RG2 transduced tumors treated with PBS. In contrast to the nude mouse model, evidence of virus dissemination to the systemic organs after intracranial injection was not detected using RT-PCR. CONCLUSIONS The RCR-mediated suicide gene therapy described in this paper effectively transduced malignant gliomas in an immunocompetent in vivo rodent model, prolonging survival, without evidence of severe intracranial inflammation, and without local transduction of normal brain cells or systemic organs.
Monetary Policy and Performance of the Oil-Exporting Gulf Cooperation Council Countries

Price stability is the goal of the monetary policy of the oil-exporting Gulf Cooperation Council (GCC) countries. Estimation results for the period 1992:1 to 2009:3 indicate that the GCC countries, with the exception of Qatar and UAE during a few quarters of 2007 and 2008, heavily sterilize the impact of the changes in foreign reserves on the domestic base money and the goal of price stability in general is maintained.
Autolysis and Autoaggregation in Pseudomonas aeruginosa Colony Morphology Mutants

ABSTRACT Two distinctive colony morphologies were noted in a collection of Pseudomonas aeruginosa transposon insertion mutants. One set of mutants formed wrinkled colonies of autoaggregating cells. Suppressor analysis of a subset of these mutants showed that this was due to the action of the regulator WspR and linked this regulator (and the chemosensory pathway to which it belongs) to genes that encode a putative fimbrial adhesin required for biofilm formation. WspR homologs, related in part by a shared GGDEF domain, regulate cell surface factors, including aggregative fimbriae and exopolysaccharides, in diverse bacteria. The second set of distinctive insertion mutants formed colonies that lysed at their center. Strains with the most pronounced lysis overproduced the Pseudomonas quinolone signal (PQS), an extracellular signal that interacts with quorum sensing. Autolysis was suppressed by mutation of genes required for PQS biosynthesis, and in one suppressed mutant, autolysis was restored by addition of synthetic PQS. The mechanism of autolysis may involve activation of the endogenous prophage and phage-related pyocins in the genome of strain PAO1. The fact that PQS levels correlated with autolysis suggests a fine balance in natural populations of P. aeruginosa between survival of the many and persistence of the few.
Three Axioms on Open Innovation and a (Non-) Parametric Application to the Entrepreneurial Case

After a brief discussion of the economics and resource-based principles underlying the open innovation (OI) paradigma we empirically investigate the impact of open innovation and alike activities on entrepreneurial knowledge and firm growth. For these purposes we use parametric as well as non-parametric techniques on panel data of US-entrepreneurs (2005-2007), the latter allowing for the analysis of multiple outputs maximization problems with multiple inputs in efficiency terms relaxing linearity and distributional assumptions of general regression estimation. We find that outside - in processes of OI significantly increase both dimensions of growth while inside-out processes (weakly) decrease firm growth. For efficient observations within the sample the knowledge production frontier shifts from proprietary innovation sources of information (i.e. R&D staff) towards higher levels of use on external sources (i.e. IP-licensing-in) over time. When firm size (or employment generation) is included as an output goal - next to the stock of knowledge - we observe minor efficiency gains over time whereby a mixed pattern of (internal and external) information sources rather than an exclusive use becomes more dominant with increasing firm size. Additionally, the efficient design of coupled processes for firm growth and knowledge production tends to shift, in particular for very small entities, from internal capacity-building objectives, that is related to the use of outside-in processes, to a dominant external exploitation pattern of proprietary knowledge assets, that is related to the use of inside-out processes.
Preclinical immunogenicity and safety of a Group A streptococcal M protein-based vaccine candidate

ABSTRACT Streptococcus pyogenes (group A streptococcus, GAS) causes a wide range of clinical manifestations ranging from mild self-limiting pyoderma to invasive diseases such as sepsis. Also of concern are the post-infectious immune-mediated diseases including rheumatic heart disease. The development of a vaccine against GAS would have a large health impact on populations at risk of these diseases. However, there is a lack of suitable models for the safety evaluation of vaccines with respect to post-infectious complications. We have utilized the Lewis Rat model for cardiac valvulitis to evaluate the safety of the J8-DT vaccine formulation in parallel with a rabbit toxicology study. These studies demonstrated that the vaccine did not induce abnormal pathology. We also show that in mice the vaccine is highly immunogenic but that 3 doses are required to induce protection from a GAS skin challenge even though 2 doses are sufficient to induce a high antibody titer.
Two Distinct mtDNA Lineages among Captive African Penguins in Japan

ABSTRACT The African penguin (Spheniscus demersus) is one of the world’s most endangered seabirds. In Japan, although the number of African penguins in captivity continues to increase, genetic data have not been collected for either wild or captive populations. To reveal genetic diversity and characterization in captive African penguins, we analyzed the nucleotide sequences of mitochondrial DNA (mtDNA) from a sample of 236 African penguins. Analysis of 433 bp of the control region and 1,140 bp of cytochrome b sequences revealed the existence of two mtDNA clades. Control region haplotypes were much more divergent (d=3.39%) between the two clades than within each clade. The divergence of these clades may reflect differences at the subspecies or geographical population level in African penguins. These findings suggest that at least two distinct maternal lineages exist in the wild populations of the African penguin.