Influence of Aeration Method on Gaseous Emissions and the Losses of the Carbon and Nitrogen during Cow Manure Composting

The objective of this research was to explore the effects of different aeration methods on NH3 and greenhouse gas (GHG) emissions and the losses of carbon and nitrogen from composting of cow manure and corn stalks in the laboratory-scale reactors. Here, we designed three treatments, including continuous aerated treatment C1 (aeration rates 0.21 L·kg−1 dry matter (DM)·min−1) and intermittent aerated treatments I1 (aeration rates 0.42 L·kg−1 DM·min−1; aerate 10 min, stop 10 min) and I2 (aeration rates 0.84 L·kg−1 DM·min−1; aerate 5 min, stop 15 min). The results showed that the physicochemical parameters (temperature, pH values, and germination index) of composting products met the requirements of maturity and sanitation. Compared with continuous aerated treatment C1, the cumulative NH3 emissions of I1 and I2 treatments decreased by 24.37% and 19.27%, while the cumulative CO2 emissions decreased by 13.01% and 20.72%. On the contrary, the cumulative N2O emissions of I1 and I2 treatments increased by 22.22% and 43.14%. CO2 emission was the principal pathway for the TOC losses, which comprised over 65% of TOC losses. C1 treatment had the highest TOC losses due to its highest cumulative CO2 emissions. The TN losses of I1 and I2 treatments reduced 9.07% and 6.1% compared to C1 treatment, so the intermittent aerated modes could reduce the TN loss. Due to the potential for mitigation of gaseous emissions, I1 treatment was recommended to be used in aerobic composting of cow manure.

Signaling Input from Divergent Pathways Subverts Malignant B-Cell Transformation

Background and significance: Normal B-cells constantly exchange information with their environment and depend on external cues for proliferation and survival that engage multiple divergent pathways (e.g. cytokine receptors; B-cell receptor, BCR). The dependency of normal B-cells on signaling input from a diverse repertoire of surface receptors is in contrast to transforming oncogenes that engage one single pathway. Beyond the established concept that diverse signal input from multiple cell surface receptors becomes dispensable in transformed cells, we here provide evidence that inactivation of divergent pathways that are not aligned with the principal oncogenic driver represents a critical step during malignant transformation. Tracking early stages of leukemia-initiation, we identified convergence on one principal oncogenic driver and inactivation of diverging pathways as critical events during B-cell transformation. Our results support a scenario in which reactivation of divergent and potentially conflicting signaling pathways represents a powerful barrier to malignant transformation. Here we studied the interaction of STAT5- and ERK-signaling pathways during normal B-cell development and malignant B-cell transformation, and found that convergence on one principal oncogenic driver represents a critical event during B cell transformation and a previously unrecognized vulnerability. Results: Our analysis of 987 patient-derived B-cell acute lymphoblastic leukemia leukemia (B-ALL) samples revealed that individual mutations did not promote leukemogenesis unless they converged on one single oncogenic pathway. Mutations that were not aligned with the central oncogenic driver would activate divergent pathways and subvert malignant transformation. Oncogenic lesions in B-ALL frequently mimic survival and proliferation signals downstream of cytokine receptors (STAT5) or the B cell receptor (ERK). STAT5- (286 cases) and ERK- (386 cases) activating lesions were frequently found but rarely co-occurred in the same sample (35 cases; P=2.5E-16). Single-cell mutation and phosphoprotein analyses revealed that even in these rare cases, oncogenic STAT5- or ERK-activation were mutually exclusive and segregated to competing clones. STAT5 and ERK engaged opposing biochemical and transcriptional programs orchestrated by MYC and BCL6, respectively. Genetic reactivation of the divergent (suppressed) pathway came at the expense of the principal oncogenic driver and reversed malignant transformation. Conversely, Cre-mediated deletion of divergent pathway components triggered leukemia-initiation and accelerated development of fatal disease. Thus, persistence of divergent signaling pathways represents a powerful barrier to malignant transformation and convergence on one principal driver defines a key event during leukemia-initiation. Proof-of-concept studies in patient-derived B-ALL cells revealed that small molecule agonists of STAT5 or ERK to reactivate the suppressed divergent circuits subvert oncogenic signaling and strongly synergized with direct inhibition of the principal oncogenic driver. Hence, pharmacological reactivation of divergent pathways can be leveraged as a previously unrecognized strategy to deepen treatment responses and to overcome drug-resistance. Current treatment approaches for drug-resistant cancer are focused on drug-combinations to suppress the central oncogenic driver and multiple alternative pathways. Here, we introduce a concept based on inhibition of the principal driver combined with pharmacological reactivation of divergent pathways Conclusions: These results provide evidence that inactivation of divergent pathways that are not aligned with the principal oncogenic driver represents a critical step during malignant transformation. Unlike B-ALL, where reactivation of a divergent pathway suppresses the principal pathway and compounds toxicity, activation of an alternative pathway in solid tumors represents a route for survival and drug resistance. While current treatment approaches for drug-resistant cancer are focused on drug-combinations to inhibit multiple pathways, we introduce a scenario that is based on inhibition of the principal pathway combined with reactivation of divergent pathways. Figure Disclosures Wiita: UCSF: Patents & Royalties; Indapta Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Protocol Intelligence: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Izraeli:sightdx: Consultancy; novartis: Honoraria; prime oncology: Speakers Bureau. Weinstock:Celgene: Research Funding; Verastem Oncology: Research Funding.

Current Perspectives in Cancer Immunotherapy

Different immunotherapeutic approaches have proved to be of significant clinical value to many patients with different types of advanced cancer. However, we need more precise immunotherapies and predictive biomarkers to increase the successful response rates. The advent of next generation sequencing technologies and their applications in immuno-oncology has helped us tremendously towards this aim. We are now moving towards the realization of personalized medicine, thus, significantly increasing our expectations for a more successful management of the disease. Here, we discuss the current immunotherapeutic approaches against cancer, including immune checkpoint blockade with an emphasis on anti-PD-L1 and anti-CTLA-4 monoclonal antibodies. We also analyze a growing list of other co-inhibitory and co-stimulatory markers and emphasize the mechanism of action of the principal pathway for each of these, as well as on drugs that either have been FDA-approved or are under clinical investigation. We further discuss recent advances in other immunotherapies, including cytokine therapy, adoptive cell transfer therapy and therapeutic vaccines. We finally discuss the modulation of gut microbiota composition and response to immunotherapy, as well as how tumor-intrinsic factors and immunological processes influence the mutational and epigenetic landscape of progressing tumors and response to immunotherapy but also how immunotherapeutic intervention influences the landscape of cancer neoepitopes and tumor immunoediting.

Self-Regeneration Performance and Characterization of Silver-Containing Activated Carbon Fibers Coated by Titanium Dioxide

In this study, wood-based activated carbon fibers (WACF) were modified by Ag nanoparticles (AgNPs) and TiO2 films. The coating of TiO2 films decreased the AgNPs agglomeration and exfoliation on WACF. As the soaking concentration of AgNO3 solution (Sconc) increased, AgNPs size and content increased, while the pore volume (especially micropore volume) of fibers reduced. However, at higher Sconc in the range of 0.2 to0.4 mol/L, only slight variations in AgNPs content and pore structure were observable for WACF/TiO2/Ag (Ag-containing WACF coated by TiO2 film). WACF/TiO2/Ag-0.1 (0.1 was the soaking concentration of AgNO3 solution, mol/L) represented the best self-regeneration performance under the visible light irradiation. The self-regeneration performance of WACF/TiO2/Ag was determined by the synergistic effects of two factors: adsorption and photodegradation. The abundant pores of WACF/TiO2/Ag-0.1 increased the methylene blue (MB) concentration of TiO2 surrounding and facilitated the MB photodegradation. Meanwhile, their suitable Ag content enhanced MB photodegradation. Furthermore, the principal pathway of a chemical reaction between Ag+ and WACF was interpreted based on the data of surface elemental constituents and surface functional groups.

Groundwater Monitoring and Plume Discharge Zone Characterization for the NRX Radiostrontium Plume at Chalk River Laboratories

Groundwater is the principal pathway for the migration of most radiological and non-radiological compounds from past and present operating areas at Atomic Energy of Canada Limited’s Chalk River Laboratories (CRL). The CRL Groundwater Monitoring Program (GWMP) was established to measure the groundwater quality around the perimeters of areas affected, or potentially affected, by groundwater plumes. One of these is the NRX Rod Bays plume, a legacy plume that originated from the fuel storage bays of the National Research Experimental (NRX) reactor. This plume contains primarily 90Sr migrating along the groundwater flow system to the Ottawa River. A characterization study of the shoreline region was completed recently to map the plume discharge zone by collecting samples from mini-piezometers and groundwater seeps (springs) during a period of low river level. Analysis of discharging groundwaters determined that the 90Sr concentrations were very similar to those sampled from nearby (upgradient) GWMP monitoring wells. With this favorable correlation, the high density of seep and mini-piezometer sampling along the shoreline allowed refinements to be made in defining the northerly and southerly boundaries of the radiostrontium plume. The seep and mini-piezometer sampling also provided evidence that the monitoring wells sampled routinely within the CRL GWMP are positioned appropriately for providing representative sampling of the plume. Shoreline seep and mini-piezometer sampling can lead to refinements in the conceptual site model for plumes with limited effort and cost. The supplemental characterization work can also potentially identify other targets for routine groundwater monitoring.

Wavelet Deconvolution to Improving Log Vertical Resolution

Improving log vertical resolution is the principal pathway to enhance identification capability for the thin-layers. This paper introduces the method which is based on the wavelet transform and the deconvolution to improve log resolution. First, gain the sub-band information on the different scales after logging curve is decomposed by wavelet. Then the detailed coefficients on the third scale are processed with deconvolution filtering, and the detailed coefficients on the first scale are dealt with threshold denoising. At last, reconstruct the logging curve whose resolution is improved. The processed results of two wells’ logs indicate that the log vertical resolution has been improved obviously using this method, which can satisfy the demands of thin-layer evaluation.

Targeting the Interleukin-6/Jak/Stat Pathway in Human Malignancies

The Janus kinase/signal transducer and activator of transcription (Jak/Stat) pathway was discovered 20 years ago as a mediator of cytokine signaling. Since this time, more than 2,500 articles have been published demonstrating the importance of this pathway in virtually all malignancies. Although there are dozens of cytokines and cytokine receptors, four Jaks, and seven Stats, it seems that interleukin-6–mediated activation of Stat3 is a principal pathway implicated in promoting tumorigenesis. This transcription factor regulates the expression of numerous critical mediators of tumor formation and metastatic progression. This review will examine the relative importance and function of this pathway in nonmalignant conditions as well as malignancies (including tumor intrinsic and extrinsic), the influence of other Stats, the development of inhibitors to this pathway, and the potential role of inhibitors in controlling or eradicating cancers.

Influence of Zeolite Dose on Eliminating Nitrogen Load of Europhia Sediment Capping with Active Barrier System (ABS)

This study investigated to eliminate the nitrogen load of sediment from Yangzhou ancient canal capping with an active barrier system (ABS) using two kinds of zeolite with five different coverage densities. For ABS capping with zeolite F1 when the zeolite dose is low (0.21 kg/m2 and 0.62 kg/m2), it is found that ABS failed to achieve good control in preventing N release in the entrophic sediments as total nitrogen (TN) concentrations of overlying water were increased to 3.76 mg/L and 3.13 mg/L, respectively after 16 days. However, when zeolite density was increased to 1.04 kg/m2, TN concentration of overlying water decreased to 1.94 mg/L and TN removal efficiency is up to 50% after 16 days. For ABS capping with zeolite F2 TN concentration of overlying water is reported to descend in both low dose and high dose series. It is found that zeolite F2 is unfit for remediation of sediments from ancient Canal in Yangzhou because the ability in preventing release of ammonia nitrogen from sediments is weak. A possible explanation is that microorganism attaching on surface of two zeoltes differs to cause large difference of removal capacity between zeolite F1 and zeolite F2. It is found that nitrification and denitrification is the principal pathway for the former one while nitrite accumulation appears in the latter. To sum up, the capacity of eliminating TN load by zeolite F1 is stronger than that by zeolite F2, the optimum capping density of zeolite F1 is 1.04 kg/m2.