Investigation of the temperature homogeneity of die melt flows in polymer extrusion

Polymer extrusion is fundamental to the processing of polymeric materials and melt flow temperature homogeneity is a major factor which influences product quality. Undesirable thermal conditions can cause problems such as melt degradation, dimensional instability, weaknesses in mechanical/optical/geometrical properties, and so forth. It has been revealed that melt temperature varies with time and with radial position across the die. However, the majority of polymer processes use only single‐point techniques whose thermal measurements are limited to the single point at which they are fixed. Therefore, it is impossible for such techniques to determine thermal homogeneity across the melt flow. In this work, an extensive investigation was carried out into melt flow thermal behavior of the output of a single extruder with different polymers and screw geometries over a wide range of processing conditions. Melt temperature profiles of the process output were observed using a thermocouple mesh placed in the flow and results confirmed that the melt flow thermal behavior is different at different radial positions. The uniformity of temperature across the melt flow deteriorated considerably with increase in screw rotational speed while it was also shown to be dependent on process settings, screw geometry, and material properties. Moreover, it appears that the effects of the material, machine, and process settings on the quantity and quality of the process output are heavily coupled with each other and this may cause the process to be difficult to predict and variable in nature. POLYM. ENG. SCI., 54:2430–2440, 2014. © 2013 Society of Plastics Engineers     

A Toxoplasma gondii Oxopurine Transporter Binds Nucleobases and Nucleosides Using Different Binding Modes

Toxoplasma gondii is unable to synthesize purines de novo, instead salvages them from its environment, inside the host cell, for which they need high affinity carriers. Here, we report the expression of a T. gondii Equilibrative Nucleoside Transporter, Tg244440, in a Trypanosoma brucei strain from which nucleobase transporters have been deleted. Tg244440 transported hypoxanthine and guanine with similar affinity (K_m ~1 µM), while inosine and guanosine displayed K_i values of 4.05 and 3.30 µM, respectively. Low affinity was observed for adenosine, adenine, and pyrimidines, classifying Tg244440 as a high affinity oxopurine transporter. Purine analogues were used to probe the substrate-transporter binding interactions, culminating in quantitative models showing different binding modes for oxopurine bases, oxopurine nucleosides, and adenosine. Hypoxanthine and guanine interacted through protonated N1 and N9, and through unprotonated N3 and N7 of the purine ring, whereas inosine and guanosine mostly employed the ribose hydroxy groups for binding, in addition to N1H of the nucleobase. Conversely, the ribose moiety of adenosine barely made any contribution to binding. Tg244440 is the first gene identified to encode a high affinity oxopurine transporter in T. gondii and, to the best of our knowledge, the first purine transporter to employ different binding modes for nucleosides and nucleobases.     

Male Rat Offspring Are More Impacted by Maternal Obesity Induced by Cafeteria Diet than Females—Additive Effect of Postweaning Diet

Maternal obesity increases the risk of health complications in offspring, but whether these effects are exacerbated by offspring exposure to unhealthy diets warrants further investigation. Female Sprague-Dawley rats were fed either standard chow (n = 15) or ‘cafeteria’ (Caf, n = 21) diets across pre-pregnancy, gestation, and lactation. Male and female offspring were weaned onto chow or Caf diet (2–3/sex/litter), forming four groups; behavioural and metabolic parameters were assessed. At weaning, offspring from Caf dams were smaller and lighter, but had more retroperitoneal (RP) fat, with a larger effect in males. Maternal Caf diet significantly increased relative expression of ACACA and Fasn in male and female weanling liver, but not CPT-1, SREBP and PGC1; PPARα was increased in males from Caf dams. Maternal obesity enhanced the impact of postweaning Caf exposure on adult body weight, RP fat, liver mass, and plasma leptin in males but not females. Offspring from Caf dams appeared to exhibit reduced anxiety-like behaviour on the elevated plus maze. Hepatic CPT-1 expression was reduced only in adult males from Caf fed dams. Post weaning Caf diet consumption did not alter liver gene expression in the adult offspring. Maternal obesity exacerbated the obesogenic phenotype produced by postweaning Caf diet in male, but not female offspring. Thus, the impact of maternal obesity on adiposity and liver gene expression appeared more marked in males. Our data underline the sex-specific detrimental effects of maternal obesity on offspring.     

Lignin solvated in zwitterionic Good's buffers displays antibacterial synergy against Staphylococcus aureus

The volume of industrial lignin is expected to increase with the deployment of biorefineries that convert lignocellulosic biomass to renewable chemicals and fuels. Interest in using lignin for value-added biomedical applications requires understanding of its effects on mammalian and microbial cells, which has been impaired by the toxicity of the solvents used to solubilize lignin. In this study, lignin is solvated in zwitterionic Good's buffers compatible with culture media. Up to 100 mg lignin can be solvated in 1 ml of 3-morpholinopropane-1-sulfonic acid (MOPS, pH 7.2) within 60 min at room temperature, whereby MOPS acts as a chaotropic agent. The addition of MOPS-solvated lignin to cultures of Staphylococcus aureus UAMS-1 containing a subinhibitory concentration of tunicamycin reduced growth more than 99% compared to tunicamycin alone, making lignin of interest as an antibiotic adjuvant. This effect of lignin is attributed to damage to the bacterial cell membrane.     

In Silico/In Vitro Hit-to-Lead Methodology Yields SMYD3 Inhibitor That Eliminates Unrestrained Proliferation of Breast Carcinoma Cells

SMYD3 is a lysine methyltransferase that regulates the expression of over 80 genes and is required for the uncontrolled proliferation of most breast, colorectal, and hepatocellular carcinomas. The elimination of SMYD3 restores normal expression patterns of these genes and halts aberrant cell proliferation, making it a promising target for small molecule inhibition. In this study, we sought to establish a proof of concept for our in silico/in vitro hit-to-lead enzyme inhibitor development platform and to identify a lead small molecule candidate for SMYD3 inhibition. We used Schrodinger^® software to screen libraries of small molecules in silico and the five compounds with the greatest predicted binding affinity within the SMYD3 binding pocket were purchased and assessed in vitro in direct binding assays and in breast cancer cell lines. We have confirmed the ability of one of these inhibitors, Inhibitor-4, to restore normal rates of cell proliferation, arrest the cell cycle, and induce apoptosis in breast cancer cells without affecting wildtype cell behavior. Our results provide a proof of concept for this fast and affordable small molecule hit-to-lead methodology as well as a promising candidate small molecule SMYD3 inhibitor for the treatment of human cancer.     

Solution Structure and Constrained Molecular Dynamics Study of Vitamin B12 Conjugates of the Anorectic Peptide PYY(3–36)

Vitamin B₁₂–peptide conjugates have considerable therapeutic potential through improved pharmacokinetic and/or pharmacodynamic properties imparted on the peptide upon covalent attachment to vitamin B₁₂ (B₁₂). There remains a lack of structural studies investigating the effects of B₁₂ conjugation on peptide secondary structure. Determining the solution structure of a B₁₂–peptide conjugate or conjugates and measuring functions of the conjugate(s) at the target peptide receptor may offer considerable insight concerning the future design of fully optimized conjugates. This methodology is especially useful in tandem with constrained molecular dynamics (MD) studies, such that predictions may be made about conjugates not yet synthesized. Focusing on two B₁₂ conjugates of the anorectic peptide PYY(3–36), one of which was previously demonstrated to have improved food intake reduction compared with PYY(3–36), we performed NMR structural analyses and used the information to conduct MD simulations. The study provides rare structural insight into vitamin B₁₂ conjugates and validates the fact that B₁₂ can be conjugated to a peptide without markedly affecting peptide secondary structure.     

适应与抵制：越南为应对气候变化采取的措施

首先,以当前应对气候变化的措施发展的批判性立场为切入点,提出一种对于世界范围的景观越来越适用、近乎通用的“工具箱”假设。它提出了一种逻辑上的反思并开拓了具有在相似内容中反复提炼出来的一系列地理与社会文化原则的设计方案。它否认空间的普遍性意义和逐渐增长的对于效能评估标准的依赖,反而强调文化适用性与地理特殊性的影响力。为证明这些假设,以近年来作者和他人协同越南合作伙伴设计的越南当地项目为重点。最终,针对气候变化制定六大主题。这些主题将细致分析周围景观的场域特定和自然逻辑作为基础,而这一逻辑又与其生态基础以及社会和文化密不可分。提出的一系列策略有助于缩小经济与生态、文化与自然、城市主义与景观之间的分歧,同时适应气候变化带来的新挑战,并抵制同质化的应对措施。     

Particle loss: An initial investigation into size effects and stress-dilatancy

Drained triaxial tests have been performed to explore the effect of particle loss on shearing behaviour and critical states in granular mixtures. The mixtures comprise Leighton Buzzard sand (d₅₀ = 0.8 mm), to which was added 15% by mass of salt particles of different nominal sizes: 0.063 mm, 0.25 mm and 0.5 mm. Shearing behaviours before and after particle loss (by dissolution) were compared. A good fit is observed between the test data and a stress-dilatancy relationship for the post-dissolution tests, highlighting the ability of the stress-dilatancy analysis as a means to interpret the effects of particle loss on shearing. It was noted that critical state strength parameter M is determined by the post-dissolution grading regardless of size of removed particle. However, the duration of contractant volumetric strain increased with the larger removed particles (0.25 mm & 0.5 mm) even when initial specific volumes were virtually identical. It is suggested that a loose volumetric state is reached if the sand particle network is initially disrupted by the amount and/or size of salt particles, which following dissolution results in structural or fabric phenomena that are not reflected in scalar volumetric measures such as specific volume.     

Performance evaluation of canine-associated Bacteroidales assays in a multi-laboratory comparison study

The contribution of fecal pollution from dogs in urbanized areas can be significant and is an often underestimated problem. Microbial source tracking methods (MST) utilizing quantitative PCR of dog-associated gene sequences encoding 16S rRNA of Bacteroidales are a useful tool to estimate these contributions. However, data about the performance of available assays are scarce. The results of a multi-laboratory study testing two assays for the determination of dog-associated Bacteroidales (DogBact and BacCan-UCD) on 64 single and mixed fecal source samples created from pooled fecal samples collected in California are presented here. Standardization of qPCR data treatment lowered inter-laboratory variability of sensitivity and specificity results. Both assays exhibited 100% sensitivity. Normalization methods are presented that eliminated random and confirmed non-target responses. The combination of standardized qPCR data treatment, use of normalization via a non-target specific Bacteroidales assay (GenBac3), and application of threshold criteria improved the calculated specificity significantly for both assays. Such measures would reasonably improve MST data interpretation not only for canine-associated assays, but for all qPCR assays used in identifying and monitoring fecal pollution in the environment.