Haploinsufficiency of a Circadian Clock Gene Bmal1 (Arntl or Mop3) Causes Brain-Wide mTOR Hyperactivation and Autism-like Behavioral Phenotypes in Mice

Approximately 50–80% of children with autism spectrum disorders (ASDs) exhibit sleep problems, but the contribution of circadian clock dysfunction to the development of ASDs remains largely unknown. The essential clock gene Bmal1 (Arntl or Mop3) has been associated with human sociability, and its missense mutation is found in ASD. Our recent study found that Bmal1-null mice exhibit a variety of autism-like phenotypes. Here, we further investigated whether an incomplete loss of Bmal1 function could cause significant autism-like behavioral changes in mice. Our results demonstrated that heterozygous Bmal1 deletion (Bmal1^+/−) reduced the Bmal1 protein levels by ~50–75%. Reduced Bmal1 expression led to decreased levels of clock proteins, including Per1, Per2, Cry 1, and Clock but increased mTOR activities in the brain. Accordingly, Bmal1^+/− mice exhibited aberrant ultrasonic vocalizations during maternal separation, deficits in sociability and social novelty, excessive repetitive behaviors, impairments in motor coordination, as well as increased anxiety-like behavior. The novel object recognition memory remained intact. Together, these results demonstrate that haploinsufficiency of Bmal1 can cause autism-like behavioral changes in mice, akin to those identified in Bmal1-null mice. This study provides further experimental evidence supporting a potential role for disrupted clock gene expression in the development of ASD.     

A sustainability root cause analysis methodology and its application

In the design of chemical/energy production systems, a major challenge is to identify the bottleneck issues and improve its sustainability effectively. Due to the multi-dimensional feature of sustainability, how to account for the impacts of various design factors and the cause-and-effect relationships can be very difficult. This paper will present a sustainability root cause analysis method based on the combination of Pareto Analysis and Fishbone diagram. The sustainability of the process is assessed incorporating economic, environmental, societal and efficiency concerns.This methodology is able to help the designers focus the attention on the most important fundamental causes, discover opportunities for sustainability improvement and provide critical guidance to design for sustainability. The efficacy of this methodology will be demonstrated through a case study on a biodiesel production technology.     

Effect of Halloysite Nanotubes as Novel Nanofiller on Peroxide- and Electron Beam Radiation-Initiated Polyphosphazene Elastomer

A tubelike, naturally occurring halloysite clay mineral (HNTs) incorporated polyphosphazene (PPZ) elastomeric nanocomposites had been electron beam radiated and thermally treated for certain applications. To improve the dispersion of raw HNTs (H), an organosilane modifier had been exploited. Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) technique were utilized for plausible interaction and intercalation. The efficiency of electron beam radiation over chemical initiation for intra and inter chain network formation within the resin was substantiated through oil and solvent resistance studies. Effective delay in mass transport as compared to the virgin elastomer was observed through thermal analysis.     

Observations of solid–liquid systems in anchor agitated vessels

Although process development is often done in well agitated vessels (e.g. with a retreat curve, pitched blade turbine etc.), there are a sizeable number of contract manufacturers’ still deploying a significant number of anchor agitated process units. For the purpose of observing the Zwietering constant value ‘S’ and few industrially important solid–liquid systems, we conducted extensive suspension experiments with anchor agitated vessels for varying D/T ratios (0.74 and 0.73). In this study, Zwietering's N_js (just suspension speed) and the corresponding ‘S’ factor were obtained for each system over a range of solid loadings. We found that the Zwietering constant was strongly dependent on the nature of the solid–liquid system; i.e. different systems had different ‘S’ values for the same geometrical configuration.     

Atomistic modeling of the effect of codoping on the atomistic structure of interfaces in α-alumina

Sintering aids or dopants have often been used successfully to limit the grain growth of alumina during sintering. Recently codoping of alumina with transition elements has been reported to produce additional effects in comparison to single doping in enhancement of creep and real in-line transmittance of light. The current study attempts to address the issue of the atomistic mechanism behind these experimentally observed codoping effects. The effect of codoping on the atomistic structure of a series of La–Y, Mg–Y, La–Mg codoped α-alumina interfaces was studied using energy minimization calculations. The segregation energy for single doping as well as codoping is negative for all the surfaces and grain boundaries. While, there is no significant energetic gain for La–Y cosegregation in comparison to single doping whereas segregation energies for Mg–Y and Mg–La codoping is more negative than single doping. A specific arrangement of dopants (associative effect) is also observed in La–Y codoped interfaces. Both mechanisms can thus contribute to the improved microstructures and properties.     

Constrained nonlinear optimization for solubility parameters of poly(lactic acid) and poly(glycolic acid)—validation and comparison

An optimization technique has been proposed to determine Hansen solubility parameters (HSP) and radius of interaction (R) of PLA and PGA; objective function to be minimized being radius of interaction (R), and the constraints being that the solvents should be within and nonsolvents outside the interaction sphere. The proposed method has been validated and found to be most reliable. The values of HSP (δ_d, δ_p, δ_h) and R for PLA have been obtained as ((18.50, 9.70, 6.00) and 10.50) (J/cc)^0.5 at 25 °C; and those of PGA as ((17.70, 6.21, 12.50) and 1.92) (J/cc)^0.5 at 80 °C. For formulating the nonlinear inequality constraints known HSP data for 20 solvents and seven nonsolvents have been used for PLA at 25 °C; similarly HSP data for three newly found solvents (phenol, m-cresol and 4-chlorophenol), and five nonsolvents have been used for PGA at 80 °C. Established methods have been used for comparison. HSP and R have been directly compared using the 3D intrinsic viscosity and classical methods. Indirectly the total solubility parameter δ has been compared with the values obtained from the intrinsic viscosity 1D approach and group contribution method using Fedors and van Krevelen correlations. The 1D approach has led to an empirical correlation for intrinsic viscosities of PLA and PGA.     

Epoxy‐montmorillonite clay nanocomposites: Synthesis and characterization

Nanocomposites of epoxy resin with montmorillonite clay were synthesized by swelling of different proportions of the clay in a diglycidyl ether of bisphenol‐A followed by in situ polymerization with aromatic diamine as a curing agent. The montmorillonite was modified with octadecylamine and made organophilic. The organoclay was found to be intercalated easily by incorporation of the epoxy precursor and the clay galleries were simultaneously expanded. However, Na‐montmorillonite clay could not be intercalated during the mixing or through the curing process. Curing temperature was found to provide a balance between the reaction rate of the epoxy precursor and the diffusion rate of the curing agent into the clay galleries. The cure kinetics were studied by differential scanning calorimetry. The exfoliation behavior of the organoclay system was investigated by X‐ray diffraction. Thermogravimetric analysis was used to determine the thermal stability, which was correlated with the ionic exchange between the organic species and the silicate layers. The morphology of the nanocomposites was evaluated by scanning electron microscopy. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 2201–2210, 2004     

Mechanical and dynamic mechanical studies of epoxy/VAc‐EHA/HMMM IPN–jute composite systems

Epoxy [50:50 mixture of Di‐Glycidyl Ether of Bis‐Phenol A (DGEBA) and Epoxidized Novolac (EPN)] was solution blended with Vinyl Acetate‐2‐ Ethylhexylacrylate (VAc‐EHA) resin in aqueous medium, in varying weight fractions, with Hexamethoxymethylmelamine (HMMM) as a crosslinker and data was compared with a control. The present work was aimed to optimize the tensile strength, dynamic mechanical strength, impact strength, and toughness by preparing a blend followed by jute composites of a semi‐ and full interpenetrating network (IPN). In control experiments epoxy alone was crosslinked (semi‐IPN), whereas the DGEBA‐EPN and VAc‐EHA/HMMM were crosslinked separately (full‐IPN), using jute as the substrate for making composites. Composites of full‐IPN systems of epoxy/VAc‐EHA system had higher moduli and UTS than the semi‐IPN systems. Dynamic mechanical study showed that full‐IPN systems have higher T_g values than semi‐IPN systems. The impact strength increases with increasing proportions of VAc‐EHA copolymer. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 958–963, 2004     

Synthesis and Biological Evaluation of Ferrocenylquinoline as a Potential Antileishmanial Agent

The emergence of resistance against antileishmanial drugs in current use necessitates the search for new classes of antileishmanial compounds. Herein we report the design, synthesis, and evaluation of a novel ferrocenylquinoline for activity against Leishmania donovani. 7‐Chloro‐N‐[2‐(1H‐5‐ferrocenyl‐1,2,3‐triazol‐1‐yl)ethyl]quinolin‐4‐amine ( 1 ) was generated by coupling an iron(II) ethynylferrocene species with 4‐(2‐ethylazido)amino‐7‐chloroquinoline using click chemistry. The synthesized compound 1 was tested for its antileishmanial activity using both promastigote and amastigote stages of L. donovani. Compound 1 showed promising anti‐promastigote activity, with an IC₅₀ value of 15.26 μM and no cytotoxicity toward host splenocytes. From the battery of tests conducted in this study, it appears that this compound induces parasite death by promoting oxidative stress and depolarizing the mitochondrial membrane potential, thereby triggering apoptosis. These results suggest that ferrocenylquinoline 1 is a suitable lead for the development of new antileishmanial drugs.     

Synthesis and characterization of solid-phase super acid catalysts and their application for isomerization of n-alkanes

In the present work, first, the reference catalyst super acidic nanostructured sulfated zirconia (SZ) and super acidic nanostructured aluminum chloride impregnated sulfated zirconium oxides in mole ratios of Zr⁴⁺:Al³⁺ as 2:1 (ACSZ-1), 1:1 (ACSZ-2), and 1:2 (ACSZ-3) were synthesized by a simple precipitation method. The catalytic performance of these four catalysts were evaluated during the isomerization of n-hexane, n-heptane, and n-octane to their corresponding branched chain isomers at low temperature and pressure conditions. ACSZ-2 shows high activity toward isomerization of n-hexane, n-heptane, and n-octane into their corresponding branched chain isomers. The reference catalyst SZ was proved to be less effective compare to the other three synthesized ACSZ catalysts. Ammonia-temperature-programmed desorption of these two materials ensures that the super acidity of ACSZ-2 is higher than that of SZ. Atomic force microscopic and scanning electron microscopic pictures predict the nature of the surface of the catalysts. Transmission electron micrographic analysis indicates the presence of particle-bulks having average size 12–20?nm, presenting an amorphous nature and having no definite surface morphology of ACSZ-2. Fourier transform infrared provides an outline regarding different linkages and bond connectivities between atoms and groups in ACSZ-2 and SZ. After catalyst evaluation and characterization a probable reaction mechanism has been proposed theoretically. The reactivity and selectivity of ACSZ-2 and SZ as well as the order and activation energy of the isomerization reactions in presence of ACSZ-2 have been calculated. The use of ACSZ-2 is beneficial from the point of cost efficiency as well as its use is energy saving.