Search

A series of new aromatic polyamides (PAs) and copolyamides (CPAs) containing fluorene group have been synthesized through polycondensation reaction. The chemical structure was confirmed by Fourier transform infrared and proton nuclear magnetic resonance (1H NMR). PAs and CPAs exhibited the higher thermal stability ( Td15 > 378°C in nitrogen), the higher glass transition temperature ( Tg > 345°C), and excellent solubility in polar solvent. Gas transport properties of the PA and CPA membranes were investigated using different single gases (hydrogen (H2), carbon dioxide (CO2), oxygen (O2), methane (CH4), and nitrogen (N2)). We discussed the effect of chemical structure and operating temperature on gas transport properties. The results show that PA-1 containing a hexafluoroisopropylidene moiety exhibited the highest gas permeability ( PH2 = 12.71 Barrer, PCO2 = 12.26 Barrer, and PO2 = 2.62 Barrer) and reasonably good selectivity ( α(H2/N2) = 27.63, α(CO2/N2) = 26.65, and α(O2/N2) = 5.70) at 25°C and 1 atm. For all the membranes, gas permeability gradually increased with the increase in operating temperature, while the selectivity gradually decreased. These gas permeation results were well correlated with fractional free volume, interchain d-spacing ( dsp), and intermolecular interaction.

Electrochemical performance and production cost are the main concerns of electrode materials for the practical supercapacitor applications. Here we use a simple and universally applicable two-step hydrothermal treatment process to prepare the flower-like CuCo2S4 nanosheet arrays directly grown on Ni foam and employ it as binder-free and conductive-agent-free electrode for pseudocapacitors. The electrode at a current density of 5 mA cm−2 exhibits an ultrahigh capacitance of 908.9 F g−1 and at 30 mA cm−2 delivers an outstanding cycling stability with retaining 91.1% after 2000 cycles compared with its initial capacity. Furthermore, the assembled flower-like nanostructured CuCo2S4//active carbon asymmetric supercapacitor displays a specific capacitance of 93.5 F g−1 at 1 mA cm−2, an energy density of 29.2 Wh kg−1 at 127 W kg−1, as well as 126.39% capacitance retention through 2000 cycles at the high current density of 25 mA cm−2, suggesting the flower-like CuCo2S4 nanosheet arrays hold promise for practical application of high-performance supercapacitors.

In recent years, the discovery of complex dynamic systems in various fields through data-driven methods has attracted widespread attention. This method has played the role of data and has become an advantageous tool for us to study complex phenomena. In this work, we propose a framework for detecting the dynamic behavior, such as the maximum likelihood transition path, of stochastic dynamic systems from data. For the stochastic dynamic system, we need to use the Kramers-Moyal formula to convert it into a deterministic form for processing, then use the extended SINDy method to obtain the parameters of stochastic dynamic systems, and finally calculate the maximum likelihood transition path. We give two examples of stochastic dynamical systems driven by additive and multiplicative Gaussian noise, and demonstrate the validity of the method by reproducing the known dynamical system behavior.

The electromagnetic blank holder is an advanced technology for sheet metal drawing using electromagnetic force. This paper introduces the electromagnetic blank holder and its working principle. The calculations of theoretical electromagnetic force, excitation current and maximum coil turns of electromagnetic blank holder system are given. The simulation model of the electromagnetic blank holder system is established using Maxwell software. The static magnetic field simulation of the electromagnetic blank holder is carried out according to the varied size of the plate and varied exciting current of the coil. The magnetic field distribution of the blank holder and magnetic ring is shown. The magnitude values of the electromagnetic force exerted on plate, blank holder and magnetic ring is given. The research results of this paper have important theoretical help for realizing the electromagnetic blank holder of sheet metal drawing in production practice.

In this study, an intelligent strategy of predicting the maximum thinning rate is proposed. Prediction strategy is based on Back Propagation Neural Network (BPNN). Because Blank Holder Force (BHF) can effectively reflect the thinning rate of cylindrical part with flange, the nodes of which are served as the inputs of BPNN in this research. The prediction objective is to obtain corresponding the maximum thinning rate of cylindrical part, which is served as the output of BPNN. The inputs data are derived from designed several critical types of Variable Blank Holder Force (VBHF). In addition, the output data is originated from corresponding simulation results of cylindrical part drawing. The mathematical expressions of prediction process have also been given in this paper. The advantage of this novel prediction strategy is that it can rapidly and accurately obtain the thickness reduction rate of cylindrical part with flange. Eventually, the validation of the created prediction method is proved by corresponding simulations and experiments.

Fokker–Planck equations describe time evolution of probability densities of stochastic dynamical systems and play an important role in quantifying propagation and evolution of uncertainty. Although Fokker–Planck equations can be written explicitly for systems excited by Gaussian white noise, they have remained unknown in general for systems excited by multiplicative non-Gaussian white noise. In this paper, we derive explicit forms of Fokker–Planck equations for one dimensional systems modeled by Marcus stochastic differential equations under multiplicative non-Gaussian white noise. As examples to illustrate the theoretical results, the derived formula is used to obtain Fokker–Planck equations for nonlinear dynamical systems under excitation of (i) α-stable white noise; (ii) combined Gaussian and Poisson white noise, respectively.

In this study, hierarchical CuCo2O4@CuCo2O4 nanowire arrays have been directly fabricated on Ni foam via a two-step method that involves hydrothermal and calcination processes. The CuCo2O4 nanowires are fully covered by porous CuCo2O4 nanosheets. The as-prepared double-metal oxide hierarchical nanowire arrays exhibit superior redox reactivity for supercapacitors. The unique hierarchical nanowire arrays own a specific capacitance of up to 888.9 F g−1 at 2 mA cm−2, which is much higher than the specific capacitance values of simple CuCo2O4 nanowire arrays. The hierarchical CuCo2O4 nanostructure shows superior cycling stability, retaining 101.77% of the initial capacitance after 2000 cycles. Moreover, by employing CuCo2O4@CuCo2O4 as the positive electrode and active carbon (AC) as the negative electrode, an asymmetric supercapacitor (ASC) device was fabricated and it displayed an excellent electrochemical performance. The enhanced electrochemical performance is mainly due to its unique hierarchical structure, which provides good ion and electron transfer, a large number of active sites, and the synergistic effect. In view of their outstanding electrochemical performance and the cost-effective fabrication process, this unique integrated nanoarchitecture may offer great promise as superior electrodes for high-performance supercapacitors.

We investigate a quantitative bistable two-dimensional model (MeKS network) of gene expression dynamics describing the competence development in the Bacillus subtilis under the influence of Levy as well as Brownian motions. To analyze the transitions between the vegetative and the competence regions therein, two dimensionless deterministic quantities, the mean first exit time (MFET) and the first escape probability, are determined from a microscopic perspective, as well as their averaged versions from a macroscopic perspective. The relative contribution factor λ, the ratio of non-Gaussian and Gaussian noise strengths, is adopted to identify an optimum choice in these transitions. Additionally, we use a recent geometric concept, the stochastic basin of attraction (SBA), to exhibit a pictorial comprehension about the influence of the Levy motion on the basin stability of the competence state. Our main results indicate that (i) the transitions between the vegetative and the competence regions can be induced by the noise intensities, the relative contribution factor λ and the Levy motion index α; (ii) a higher noise intensity and a larger α with smaller jump magnitude make the MFET shorter, and the MFET as a function of λ exhibits one maximum value, which is a signature of the noise-enhanced stability phenomenon for the vegetative state; (iii) a larger α makes the transition from the vegetative to the adjacent competence region to occur at the highest probability. The Levy motion index α 0 ≈ 0.5 (a larger jump magnitude with a lower frequency) is an ideal choice to implement the transition to the non-adjacent competence region; (iv) there is an expansion in SBA when α decreases.

This paper focuses on studies of electromagnetic force control system of solenoid coil electromagnetic field. The mathematical relationship of electromagnetic force with power supply current of solenoid electromagnetic coil is derived. The control system of electromagnetic force is constructed, which includes an adjustable PWM power supply and a solenoid coil. Simulation model of electromagnetic force control system by Simplorer and simulation model of solenoid coil electromagnetic field by Maxwell are given. By co-simulation of Simplorer software and Maxwell software, the simulation results of current characteristics of the solenoid coil are given. At same time, the distribution of electromagnetic strength and electromagnetic force in the solenoid coil electromagnetic field are graphical shown. The research results of this paper have a good guiding significance for the simulation of other types of electromagnetic force control system.

This paper presents a method of studying electromagnetic field using Simplorer and Maxwell software. The basic principles of electromagnetic field control are discussed, including excitation power supply, magnetic field, and the relationship of between electric field and magnetic field. The ideas and steps of establishing the electromagnetic field research model using Simplorer and Maxwell software are introduced. The method of building up the model of electromagnetic coil using Maxwell software and the model of circuit of excitation power supply using Simplorer software are introduced. This paper has positive guidance and help for the research and application of electromagnetic field.

In either natural fertilization or artificial insemination, hundreds of millions of sperm are ejaculated or inseminated and then deposited in the female reproductive tract, but only a few sperm reach the ampulla or the site of fertilization. This dramatic reduction in numbers clearly highlights the obstacles that sperm must overcome in order to reach the destination for egg fertilizing. Phagocytosis of sperm by leukocytes are repeatedly observed and generally considered to be one of the most important barriers, but the mechanism of the phagocytosis of sperm remains unclear. L-selectin is constitutively expressed on leukocytes, which can influence the behaviors of leukocytes when bind to ligands. Sialic acids are found as the outer most monosaccharide, capping the majority of glycans at the sperm surface, can act as recognition molecule. Since the sialic acids are considered as ligands of L-selectin, we propose that leukocytes bind to the sperm through the L-selectin on leukocytes and sialic acid on sperm surface during the sperm phagocytosis in female reproductive tract.

In this study, we have developed a facile in situ growth process to prepare three-dimensional (3D) interconnected CuS nanowalls on Ni foam, which have a large number of nanosheets on both sides of the nanowalls. The fabrication route contains the replacement process of Cu submicrometer-sized cubes on Ni foam and subsequent in situ growth process of interconnected rough CuS nanowalls (RCuS) on Ni foam via a hydrothermal method. The RCuS electrode displays excellent performance, demonstrating a specific capacitance of 1124 F g−1 at a current density of 15 mA cm−2 and 912.5 F g−1 at 30 mA cm−2 with a good cycling ability (∼90.7% of the initial specific capacitance remained after 2000 cycles), which is much higher than that of the CuS electrode through a simple hydrothermal (HCuS), taking copper dichloride as the copper source. The excellent electrochemical performance may be attributed to the high conductivity, large specific surface, and strong bonding between nanowalls and the Ni foam. The demonstrated high specific capacity and remarkable rate performance of the CuS nanowalls, together with the flexibility of the nickel foam substrate, make the 3D nanostructured electrode ideally suited for low-cost, high-performance supercapacitors.

The efficiency optimization of asynchronous motor control system is meaningful for saving energy. The efficiency optimization principle of asynchronous motor is analyzed. Several efficiency optimization strategies are discussed. Efficiency optimization strategy of fuzzy search is proposed. This strategy is to realize minimum input power of motor by fuzzy searching for optimal rotor flux. The online fuzzy search controller is designed. Simulation model of motor control system is set up. By comparing and analysis of simulation results, the effectiveness of strategy proposed is validated.

An abrupt climatic transition could be triggered by a single extreme event, and an α-stable non-Gaussian Levy noise is regarded as a type of noise to generate such extreme events. In contrast with the classic Gaussian noise, a comprehensive approach of the most probable transition path for systems under α-stable Levy noise is still lacking. We develop here a probabilistic framework, based on the nonlocal Fokker-Planck equation, to investigate the maximum likelihood climate change for an energy balance system under the influence of greenhouse effect and Levy fluctuations. We find that a period of the cold climate state can be interrupted by a sharp shift to the warmer one due to larger noise jumps with low frequency. Additionally, the climate change for warming 1.5°C under an enhanced greenhouse effect generates a steplike growth process. These results provide important insights into the underlying mechanisms of abrupt climate transitions triggered by a Levy process.

Hematopoietic stem cells (HSCs) are the precursors of the hematopoietic system responsible for the lifelong production of blood and bone marrow. Given the emerging importance of epigenetic regulation in HSC fate decisions and malignant transformation, we investigated the role of the DNA methyltransferase Dnmt3b through genetic ablation in HSCs – either alone or in combinatorial deletion with its paralog Dnmt3a. While conditional inactivation of Dnmt3b alone in adult HSCs had minor functional impact, simultaneous deletion of Dnmt3a and Dnmt3b was synergistic resulting in a severe block in differentiation and enhanced HSC self-renewal. Dnmt3a/b-null HSCs displayed activated β-catenin signaling, partly accounting for the differentiation block. Loss of Dnmt3a in HSCs resulted in global DNA hypomethylation, but a paradoxical hypermethylation of CpG islands, most of which was eliminated in Dnmt3a/b-null HSCs. These data demonstrate distinct roles for Dnmt3b in HSC differentiation and provide unprecedented resolution into the epigenetic regulation of HSC fate decisions.

Electrode materials with graphite flake layer structure decorated with nickel oxide and nickel sulfide nanoparticles (NiO/Ni3S2) have been prepared by one-pot microwave method. When NiO/Ni3S2@graphite synthesized by microwave is compared with NiO@graphite electrode, the former obtains a high capacitance of 768 F g−1 at 1 A g−1, exceeding 72% (446 F g−1 at 1 A g−1) of the latter. After 1000 cycles of the NiO/Ni3S2@graphite electrode, the specific capacitance remained at 692 F g−1 (at 1 A g−1) with a capacitance retention of 90%. Furthermore, NiO/Ni3S2@graphite and active carbon electrodes could be assembled into asymmetric supercapacitor (ASC), which exhibited a specific capacitance of 68.5 F g−1 at 1 A g−1 in 6 M KOH solution. The NiO/Ni3S2@graphite//AC ASC also showed a relatively high energy density of 28.86 Wh kg−1, maximum power density of 0.77 kW kg−1, and exceptional cycling stability (80% retention after 2000 cycles).

For the tipping elements in the Earth’s climate system, the most important issue to address is how stable is the desirable state against random perturbations. Extreme biotic and climatic events pose severe hazards to tropical rainforests. Their local effects are extremely stochastic and difficult to measure. Moreover, the direction and intensity of the response of forest trees to such perturbations are unknown, especially given the lack of efficient dynamical vegetation models to evaluate forest tree cover changes over time. In this study, we consider randomness in the mathematical modelling of forest trees by incorporating uncertainty through a stochastic differential equation. According to field-based evidence, the interactions between fires and droughts are a more direct mechanism that may describe sudden forest degradation in the south-eastern Amazon. In modeling the Amazonian vegetation system, we include symmetric α-stable Lévy perturbations. We report results of stability analysis of the metastable fertile forest state. We conclude that even a very slight threat to the forest state stability represents L´evy noise with large jumps of low intensity, that can be interpreted as a fire occurring in a non-drought year. During years of severe drought, high-intensity fires significantly accelerate the transition between a forest and savanna state.

Supporting information. Figure S1. Schematic illustration (A) and photograph (B) of the as-fabricated NiCo2S4@NiMoO4//AC device. Figure S2. XPS spectra of the (A) survey spectrum, (B) Ni 2p, (C) Co 2p, (D) Mo 3d, (E) S 2p and (F) O 1 s of the NiCo2S4@NiMoO4 composite. Figure S3. (A) CV curves at different scan rates and (B) GCD curves at different current densities of NiCo2S4. Figure S4. Impedance Nyquist plots of the NiCo2S4@NiMoO4 hybrid electrode before and after 2000 cycles in a three-electrode system. Figure S5. CV curves of the AC electrode at different scan rates (A), GCD curves of the AC electrode at different current densities (B), the specific capacitance change of the AC electrode at different current densities (C). Figure S6. Impedance Nyquist plots of the NiCo2S4@NiMoO4//AC device before and after 2000 cycles. (DOCX 2512 kb)

Japanese encephalitis (JE), caused by Japanese encephalitis virus (JEV) infection, is the most important viral encephalitis in the world. Approximately 35,000-50,000 people suffer from JE every year, with a mortality rate of 10,000-15,000 people per year. Although the safety and efficacy of JE vaccines (inactivated and attenuated) have been demonstrated, China still accounts for 50% of the reported JE cases worldwide. In this review, we provide information about the burden of JE in mainland China and the corresponding epidemiology from 1949 to 2010, including the morbidity and mortality of JE; the age, gender, and vocational distribution of JE cases; its regional and seasonal distribution; and JE immunization. In addition, we discuss the relationships among vectors, hosts, and JEV isolates from mainland China; the dominant vector species for JEV transmission; the variety of JEV genotypes and the different biological characteristics of the different JEV genotypes; and the molecular evolution of JEV.

The time evolution of probability densities for solutions to stochastic differential equations (SDEs) without delay is usually described by Fokker-Planck equations, which require the adjoint of the infinitesimal generator for the solutions. However, Fokker-Planck equations do not exist for stochastic delay differential equations (SDDEs) since the solutions to SDDEs are not Markov processes and have no corresponding infinitesimal generators. In this paper, we address the open question of finding governing equations for probability densities of SDDEs with discrete time delays. In the governing equation, densities for SDDEs with discrete time delays are expressed in terms of those for SDEs without delay. The latter have been well studied and can be obtained by solving the corresponding Fokker-Planck equations. The governing equation is given in a simple form that facilitates theoretical analysis and numerical computation. Some example are presented to illustrate the proposed governing equations.

To investigate the species and distribution of mosquitoes and mosquito-borne arboviruses in Yuncheng city of Shanxi province, China.Mosquito samples were collected in 19 collection sites from Linyi county and Yongji city in Yuncheng city, in August, 2012. After identification and classification, all the specimens were homogenized and centrifuged to acquire supernatant before being inoculated to both C6/36 and BHK21 cells for viral isolation. Positive isolates were identified with arbovirus species-specific primers under RT-PCR, for further sequencing and phylogenetic analysis.A total of 10 455 mosquitoes of 7 species in 4 genuese were collected. The predominant mosquito species in Linyi county was Culex pipens pallens (91.96%, 3 911/4 253), but the one in Yongji city was Culex tritaeniorhynchus (72.85%, 4 518/6 202). A total of 23 strains of viruses were isolated from the mosquito pools. 15 strains from Culex tritaeniorhynchus and Culex pipens pallens were identified as genotype I Japanese encephalitis virus (JEV). Four strains from Culex pipens pallens were identified as Culex flavivirus (CxFV). Three strains from Culex pipens pallens were identified as Culex pipiens pallens densovirus (CppDNV). One strain from Armigeres subalbatus and Aedes albopictus was identified as Getah virus (GETV).Four kinds of arboviruses were isolated from the mosquito pools, including GETV and CxFV, which were isolated and documented in Shanxi province for the first time. In the city of Yuncheng, Culex tritaeniorhynchus had been the predominant species and major vector for transmitting JEV. Genotype I JEV remained the major JEV circulating in the local natural environment.

Marcus stochastic differential equations (SDEs) often are appropriate models for stochastic dynamical systems driven by non-Gaussian Lévy processes and have wide applications in engineering and physical sciences. The probability density of the solution to an SDE offers complete statistical information on the underlying stochastic process. Explicit formula for the Fokker–Planck equation, the governing equation for the probability density, is well-known when the SDE is driven by a Brownian motion. In this paper, we address the open question of finding the Fokker–Planck equations for Marcus SDEs in arbitrary dimensions driven by non-Gaussian Lévy processes. The equations are given in a simple form that facilitates theoretical analysis and numerical computation. Several examples are presented to illustrate how the theoretical results can be applied to obtain Fokker–Planck equations for Marcus SDEs driven by Lévy processes.

Basin of attraction of a stable equilibrium point is an effective concept for stability analysis in deterministic systems; however, it does not contain information on the external perturbations that may affect it. Here we introduce the concept of stochastic basin of attraction (SBA) by incorporating a suitable probabilistic notion of basin. We define criteria for the size of the SBA based on the escape probability, which is one of the deterministic quantities that carry dynamical information and can be used to quantify dynamical behavior of the corresponding stochastic basin of attraction. SBA is an efficient tool to describe the metastable phenomena complementing the known exit time, escape probability, or relaxation time. Moreover, the geometric structure of SBA gives additional insight into the system's dynamical behavior, which is important for theoretical and practical reasons. This concept can be used not only in models with small noise intensity but also with noise whose amplitude is proportional or in general is a function of an order parameter. As an application of our main results, we analyze a three potential well system perturbed by two types of noise: Brownian motion and non-Gaussian α-stable Lévy motion. Our main conclusions are that the thermal fluctuations stabilize the metastable system with an asymmetric three-well potential but have the opposite effect for a symmetric one. For Lévy noise with larger jumps and lower jump frequencies ( α=0.5) metastability is enhanced for both symmetric and asymmetric potentials.

Japanese encephalitis (JE), caused by Japanese encephalitis virus (JEV) infection, is the most important viral encephalitis in the world. Approximately 35,000-50,000 people suffer from JE every year, with a mortality rate of 10,000-15,000 people per year. Although the safety and efficacy of JE vaccines (inactivated and attenuated) have been demonstrated, China still accounts for 50% of the reported JE cases worldwide. In this review, we provide information about the burden of JE in mainland China and the corresponding epidemiology from 1949 to 2010, including the morbidity and mortality of JE; the age, gender, and vocational distribution of JE cases; its regional and seasonal distribution; and JE immunization. In addition, we discuss the relationships among vectors, hosts, and JEV isolates from mainland China; the dominant vector species for JEV transmission; the variety of JEV genotypes and the different biological characteristics of the different JEV genotypes; and the molecular evolution of JEV.

Hematopoietic stem cells replenish all the cells of the blood throughout the lifetime of an animal. Although thousands of stem cells reside in the bone marrow, only a few contribute to blood production at any given time. Nothing is known about the differences between individual stem cells that dictate their particular state of activation readiness. To examine such differences between individual stem cells, we determined the global gene expression profile of 12 single stem cells using microarrays. We showed that at least half of the genetic expression variability between 12 single cells profiled was due to biological variation in 44% of the genes analyzed. We also identified specific genes with high biological variance that are candidates for influencing the state of readiness of individual hematopoietic stem cells, and confirmed the variability of a subset of these genes using single-cell real-time PCR. Because apparent variation of some genes is likely due to technical factors, we estimated the degree of biological versus technical variation for each gene using identical RNA samples containing an RNA amount equivalent to that of single cells. This enabled us to identify a large cohort of genes with low technical variability whose expression can be reliably measured on the arrays at the single-cell level. These data have established that gene expression of individual stem cells varies widely, despite extremely high phenotypic homogeneity. Some of this variation is in key regulators of stem cell activity, which could account for the differential responses of particular stem cells to exogenous stimuli. The capacity to accurately interrogate individual cells for global gene expression will facilitate a systems approach to biological processes at a single-cell level., Synopsis The hematopoietic stem cell (HSC) has the remarkable property of being able to generate more stem cells or cells that are committed to undergo differentiation into specific blood lineages. Currently, very little is known about the specific mechanisms that underlie self-renewal or lineage commitment. Although it is possible that some of these mechanisms are influenced by the specific environment in which the HSC dwells, the ultimate fate decision has to occur at the single HSC level. The authors have developed a method that amplifies the messages from the majority of genes that are active in a single stem cell and combines it with large-scale genetic expression analysis through the use of nucleic acid microarrays. A significant fraction of these genes are found to be highly variable in an apparently very homogeneous stem cell population, which could be the substrate for differences in behavior of individual stem cells. Understanding the genetic expression events at the single-cell level would grant the ability to expand HSCs or to direct their differentiation into specific populations, both important from a therapeutic point of view. Furthermore, the same techniques can be applied to other stem cell systems to investigate their physiology.

Hematopoietic stem cells (HSCs) maintain tissue homeostasis by rapidly responding to environmental changes. Although this function is well understood, the molecular mechanisms governing this characteristic are largely unknown. We used a sequenced-based strategy to explore the role of both transcriptional and post-transcriptional regulation in HSC biology. We characterized the gene expression differences between HSCs, both quiescent and proliferating, and their differentiated progeny. This analysis revealed a large fraction of sequence tags aligned to intronic sequences, which we showed were derived from unspliced transcripts. A comparison of the biological properties of the observed spliced versus unspliced transcripts in HSCs showed that the unspliced transcripts were enriched in genes involved in DNA binding and RNA processing. In addition, levels of unspliced message decreased in a transcript-specific fashion after HSC activation in vivo. This change in unspliced transcript level coordinated with increases in gene expression of splicing machinery components. Combined, these results suggest that post-transcriptional regulation is important in HSC activation in vivo.

Background: Chronic infections and inflammatory conditions can cause bone marrow suppression and pancytopenia, a dangerous condition that impairs recovery from infection. In some chronic infections such as tuberculosis, marrow suppression has been ascribed to myelofibrosis. However, inflammatory conditions also affect hematopoietic stem cells (HSCs) themselves. HSCs are activated to proliferate and differentiate in the setting of a Mycobacterium avium infection. These responses are mediated by interferon gamma (IFNg) signaling. We hypothesized that sustained interferon signaling during a chronic infection would impair self-renewal in HSCs and lead to premature exhaustion of the stem cell compartment. Objective: To ascertain whether persistent interferon exposure in an animal model of chronic Mycobacterium avium infection leads to cell autonomous reduction in HSC number and competency. Methods: We conducted sustained infection of C57Bl/6 wild type mice with M. avium over an 8-month period. At monthly intervals, we assessed HSC number and pluripotency in a mouse model of bone marrow transplantation. In order to determine whether suppression of HSC counts was due to a cell autonomous or environmental effect, we performed Mycobacterium avium infection in chimeric mice containing mixed WT and IFNg-receptor-deficient (Ifngr1-/-) marrow. Results: After 6 months of repeated infection with M. avium, mice became anemic and leukopenic. There was a gradual decrease in the number of committed hematopoietic progenitors and a depletion of HSCs in the bone marrow by 6 months following initial infection. The bone marrow of infected animals was hypercellular and not fibrotic. Despite the overall reduction in HSC number, HSCs that remained in chronically infected animals retained full self-renewal potential even across multiple rounds of transplantation. Whereas WT marrow was suppressed in M. avium-infected chimeras, Ifngr1-/- marrow demonstrated enhanced engraftment, indicating an IFNg-dependent cell autonomous reduction in self-renewal potential. Transcriptional profiling of HSCs from M. avium-infected and control animals by RNAseq indicated that genes involved in the interferon gamma-mediated inflammatory response and genes associated with aging were differentially upregulated. Conclusions: We find that chronic interferon gamma exposure can deplete the HSC pool without inducing myelofibrosis. Further, we demonstrate that IFNg-mediated impairment in HSC self-renewal is cell-autonomous. Despite a reduction in HSC number, a subset of HSCs is protected from exhaustion and maintains self-renewal potential. Serial M. avium infection may be utilized as a mouse model for bone marrow suppression associated with inflammatory conditions, as is seen in some patients with chronic infections or autoimmune disorders. In future studies, candidate genes identified by transcriptome analysis will be assessed for their contribution to HSC exhaustion in the setting of chronic inflammation. Disclosures No relevant conflicts of interest to declare.

Abstract 2365 Background: Anemia, leucopenia, or pancytopenia is a common presenting sign in a number of chronic infectious diseases such as HIV and atypical mycobacterial infection. In order to understand the pathophysiology of pancytopenia as a complication of chronic infection, we have investigated the responses of hematopoietic stem cells (HSCs) to mycobacterial infection. We previously found that HSCs proliferate in the setting of a Mycobacterium avium infection. We hypothesized that sustained infection impairs self-renewal in HSCs and leads to premature exhaustion of the stem cell compartment. Method: Testing HSC self-renewal is nontrivial and requires serial bone marrow transplantation to measure HSC totipotency over time. Three successive rounds of bone marrow transplantation were conducted using HSCs from mice with M. avium infection. Results: HSCs from infected mice were significantly less capable of sustaining trilineage peripheral blood production after serial transplantation compared to control HSCs. These findings demonstrate that self-renewal of HSCs is compromised during chronic infection. It follows that the total number of HSCs should decline with time during sustained infection. To test this, serial monthly infection with M. avium was conducted over an 8-month period. Repeatedly infected animals showed a gradual decrease in the number of committed lymphoid and myeloid progenitors and a significant depletion of HSCs in the bone marrow by 6 months following initial infection. Transcriptional profiling of HSCs from M. avium-infected animals by RNAseq revealed previously uncharacterized potential regulators of HSC self-renewal. Conclusion: Our results demonstrate that HSC self-renewal is compromised during chronic infection, leading to exhaustion of the stem cell compartment. These findings elucidate both the basis for and possible therapeutic approaches towards hematologic complications in patients with atypical mycobacterial infection, tuberculosis, HIV, and other chronic inflammatory conditions. Disclosures: No relevant conflicts of interest to declare.