Synthesis and DFT investigation of new bismuth-containing MAX phases

The M(n + 1)AX(n) phases (M = early transition metal; A = group A element and X = C and N) are materials exhibiting many important metallic and ceramic properties. In the present study powder processing experiments and density functional theory calculations are employed in parallel to examine formation of Zr(2)(Al(1−x)Bi(x))C (0 ≤ x ≤ 1). Here we show that Zr(2)(Al(1−x)Bi(x))C, and particularly with x ≈ 0.58, can be formed from powders even though the end members Zr(2)BiC and Zr(2)AlC seemingly cannot. This represents a significant extension of the MAX phase family, as this is the first report of a bismuth-based MAX phase

The cloud aerosol interaction and precipitation enhancement experiment (CAIPEEX): Overview and preliminary results

While the demand for enhancing rainfall through cloud seeding is strong and persistent in the country, considerable uncertainty exists on the success of such an endeavour at a given location. To understand the pathways of aerosol-cloud interaction through which this might be achieved, a national experiment named Cloud Aerosol Interaction and Precipitation Enhancement EXperiment (CAIPEEX) in two phases, was carried out. The rationale of CAIPEEX, the strategy for conducting the experiment, data quality and potential for path-breaking science are described in this article. Pending completion of quality control and calibration of the CAIPEEX phase-II data, here we present some initial results of CAIPEEX phase-I aimed at documenting the prevailing microphysical characteristics of aerosols and clouds and associated environmental conditions over different regions of the country and under different monsoon conditions with the help of an instrumented research aircraft. First-time simultaneous observations of aerosol, cloud condensation nuclei (CCN) and cloud droplet number concentration (CDNC) over the Ganges Valley during monsoon season show very high concentrations (> 1000 cm-3) of CCN at elevated layers. Observations of elevated layers with high aerosol concentration over the Gangetic valley extending up to 6 km and relatively less aerosol concentration in the boundary layer are also documented. We also present evidence of strong cloud- aerosol interaction in the moist environments with an increase in the cloud droplet effective radius. Our observations also show that pollution increases CDNC and the warm rain depth, and delays its initiation. The critical effective radius for warm rain initiation is found to be between 10 and 12 μm in the polluted clouds and it is between 12 and 14 μm in cleaner monsoon clouds

Translocation-coupled DNA cleavage by the Type ISP restriction-modification enzymes

Endonucleolytic double-strand DNA break production requires separate strand cleavage events. Although catalytic mechanisms for simple dimeric endonucleases are available, there are many complex nuclease machines which are poorly understood in comparison. Here we studied the single polypeptide Type ISP restriction-modification (RM) enzymes, which cleave random DNA between distant target sites when two enzymes collide following convergent ATP-driven translocation. We report the 2.7 Angstroms resolution X-ray crystal structure of a Type ISP enzyme-DNA complex, revealing that both the helicase-like ATPase and nuclease are unexpectedly located upstream of the direction of translocation, inconsistent with simple nuclease domain-dimerization. Using single-molecule and biochemical techniques, we demonstrate that each ATPase remodels its DNA-protein complex and translocates along DNA without looping it, leading to a collision complex where the nuclease domains are distal. Sequencing of single cleavage events suggests a previously undescribed endonuclease model, where multiple, stochastic strand nicking events combine to produce DNA scission

Thermodynamics-Based Models of Transcriptional Regulation by Enhancers: The Roles of Synergistic Activation, Cooperative Binding and Short-Range Repression

Quantitative models of cis-regulatory activity have the potential to improve our mechanistic understanding of transcriptional regulation. However, the few models available today have been based on simplistic assumptions about the sequences being modeled, or heuristic approximations of the underlying regulatory mechanisms. We have developed a thermodynamics-based model to predict gene expression driven by any DNA sequence, as a function of transcription factor concentrations and their DNA-binding specificities. It uses statistical thermodynamics theory to model not only protein-DNA interaction, but also the effect of DNA-bound activators and repressors on gene expression. In addition, the model incorporates mechanistic features such as synergistic effect of multiple activators, short range repression, and cooperativity in transcription factor-DNA binding, allowing us to systematically evaluate the significance of these features in the context of available expression data. Using this model on segmentation-related enhancers in Drosophila, we find that transcriptional synergy due to simultaneous action of multiple activators helps explain the data beyond what can be explained by cooperative DNA-binding alone. We find clear support for the phenomenon of short-range repression, where repressors do not directly interact with the basal transcriptional machinery. We also find that the binding sites contributing to an enhancer's function may not be conserved during evolution, and a noticeable fraction of these undergo lineage-specific changes. Our implementation of the model, called GEMSTAT, is the first publicly available program for simultaneously modeling the regulatory activities of a given set of sequences

Attention Enhances the Retrieval and Stability of Visuospatial and Olfactory Representations in the Dorsal Hippocampus

Attention enhances the encoding and retrieval of olfactory and visuospatial representations by modulating place field stability, firing rate, and neuronal synchronization of pyramidal cells in the hippocampus

The role of proteomics in depression research

Depression is a severe neuropsychiatric disorder affecting approximately 10% of the world population. Despite this, the molecular mechanisms underlying the disorder are still not understood. Novel technologies such as proteomic-based platforms are beginning to offer new insights into this devastating illness, beyond those provided by the standard targeted methodologies. Here, we will show the potential of proteome analyses as a tool to elucidate the pathophysiological mechanisms of depression as well as the discovery of potential diagnostic, therapeutic and disease course biomarkers

In Vivo Methods to Study Uptake of Nanoparticles into the Brain

Several in vivo techniques have been developed to study and measure the uptake of CNS compounds into the brain. With these techniques, various parameters can be determined after drug administration, including the blood-to-brain influx constant (Kin), the permeability-surface area (PS) product, and the brain uptake index (BUI). These techniques have been mostly used for drugs that are expected to enter the brain via transmembrane diffusion or by carrier-mediated transcytosis. Drugs that have limitations in entering the brain via such pathways have been encapsulated in nanoparticles (based on lipids or synthetic polymers) to enhance brain uptake. Nanoparticles are different from CNS compounds in size, composition and uptake mechanisms. This has led to different methods and approaches to study brain uptake in vivo. Here we discuss the techniques generally used to measure nanoparticle uptake in addition to the techniques used for CNS compounds. Techniques include visualization methods, behavioral tests, and quantitative methods

RNA interference approaches for treatment of HIV-1 infection

HIV/AIDS is a chronic and debilitating disease that cannot be cured with current antiretroviral drugs. While combinatorial antiretroviral therapy (cART) can potently suppress HIV-1 replication and delay the onset of AIDS, viral mutagenesis often leads to viral escape from multiple drugs. In addition to the pharmacological agents that comprise cART drug cocktails, new biological therapeutics are reaching the clinic. These include gene-based therapies that utilize RNA interference (RNAi) to silence the expression of viral or host mRNA targets that are required for HIV-1 infection and/or replication. RNAi allows sequence-specific design to compensate for viral mutants and natural variants, thereby drastically expanding the number of therapeutic targets beyond the capabilities of cART. Recent advances in clinical and preclinical studies have demonstrated the promise of RNAi therapeutics, reinforcing the concept that RNAi-based agents might offer a safe, effective, and more durable approach for the treatment of HIV/AIDS. Nevertheless, there are challenges that must be overcome in order for RNAi therapeutics to reach their clinical potential. These include the refinement of strategies for delivery and to reduce the risk of mutational escape. In this review, we provide an overview of RNAi-based therapies for HIV-1, examine a variety of combinatorial RNAi strategies, and discuss approaches for ex vivo delivery and in vivo delivery

Binary systems and their nuclear explosions

Peer ReviewedPreprin

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac