pH‐Cleavable Nucleoside Lipids: A New Paradigm for Controlling the Stability of Lipid‐Based Delivery Systems

Lipid‐based delivery systems are an established technology with considerable clinical acceptance and several applications in human. Herein, we report the design, synthesis and evaluation of novel orthoester nucleoside lipids (ONLs) for the modulation of liposome stability. The ONLs contain head groups with 3′‐orthoester nucleoside derivatives featuring positive or negative charges. The insertion of the orthoester function in the NL structures allows the formation of pH‐sensitive liposomes. ONL‐based liposomes can be hydrolyzed to provide nontoxic products, including nucleoside derivatives and hexadecanol. To allow the release to be tunable at different hydrolysis rates, the charge of the polar head structure is modulated, and the head group can be released at a biologically relevant pH. Crucially, when ONLs are mixed with natural phosphocholine lipids (PC), the resultant liposome evolves toward the formation of a hexadecanol/PC lamellar system. Biological evaluation shows that stable nucleic acid lipid particles (SNALPs) formulated with ONLs and siRNAs can effectively enter into tumor cells and release their nucleic acid payload in response to an intracellular acidic environment. This results in a much higher antitumor activity than conventional SNALPs. The ability to use pH‐cleavable nucleolipids to control the stability of lipid‐based delivery systems represents a promising approach for the intracellular delivery of drug cargos.     

Cellular Internalization of Water‐Soluble Helical Aromatic Amide Foldamers

The intracellular transport of drugs and therapeutics represents one of the most exciting and challenging areas at the interface of chemistry, biology, and medicine. Most of the effort in this field so far has been devoted to the development of peptide‐based delivery systems that can translocate therapeutic agents into their intracellular targets. More recently, the use of bioinspired non‐natural foldamers has resulted in the successful delivery of cargo molecules, which possess a wide range of sizes and physicochemical properties across the cell membrane. We report herein the synthesis of aromatic amide foldamers and their biological evaluation as cell‐penetrating agents. By using a well‐established synthetic route, a series of fluorescein‐labeled cationic aryl amide conjugates has been constructed, and their cellular uptake into various human cell lines has been analyzed by flow cytometry and fluorescence microscopy. The assays revealed that longer oligomers achieve greater cellular translocation, with octamer Q8 proving to be a remarkable vehicle for all three cell lines. Biological studies have also indicated that these helices are biocompatible, thus showing promise in their application as cell‐penetrating agents and as vehicles to deliver biologically active molecules into cells.     

Optimisation of monolithic lining concepts of channel induction furnace

Abstract

For the possible energy savings and extension of the volume capacity, the monolithic lining of a channel induction furnace was optimised in the following manner. Orthogonal array method is utilised to systematically design the lining concepts, and the finite element simulations including the temperature dependent properties of monoliths are carried out to determine the temperatures and stresses during the preheating and holding. In terms of the main effect analysis materials for the monolithic lining are recommended. Moreover, a thickness–thickness–temperature isothermal map is provided to show the acceptable thickness range of working and insulating linings. Nevertheless, for the final decision the deliberate consideration for the cost effectiveness of a certain lining concept is also necessary.     

A cumulative score quality control scheme

Ncube and Woodall (1984) developed combined Shewhart­cumulative score (cuscore) quality control procedures for detecting shifts in the process mean of continuous production processes. These procedures only considered the past history of the scores but not that of the values of the quality characteristic, the sample mean. The proposed scheme takes into consideration the past history of the values of the sample mean quality characteristic and the past history of the scores. It will be shown, by average run length comparisons, that the proposed scheme performs significantly better than the standard cuscore procedures, the Shewhart procedures and cusum procedures for shifts in the process mean considered     

Adsorptive solar powered ice maker: experiments and model

A solar adsorptive ice maker model is presented and experimentally validated. In order to determine the model parameters, the identification procedure is carried out employing an experimental data base obtained from tests carried out on two adsorptive solar-powered ice-makers using a methanol/carbon pair. The packaged component, the collector–condenser, represents the main new feature of these units. The prediction is compared with results of correlations. This allows a comparison of the collector–condenser behavior in the two units since the collector–condenser of one of these units is equipped with a radiation shield. The model is then used to study daily ice production sensitivity vis-à-vis critical physical parameters of the unit and to estimate the limits of the collector–condenser technology with flat plate collectors.     

First documentation of spawning and nest guarding in the laboratory by the invasive fish,the round goby (Neogobius melanostomus)

Although the round goby, Neogobius melanostomus, is widespread in the Great Lakes and has an extended breeding season with a high reproductive rate; its spawning behaviour remains elusive. We present the first reported accounts of spawning by the round goby in the laboratory. By simulating winter conditions and restoring spring conditions, we induced round gobies to spawn in October 2007, March 2008, May 2008, and January 2009. In one case, fanning by the nest-holding male began 10 days before egg deposition and, during this period, the male rubbed secretions along the ceiling of the nest. Males were choosy about which gravid females entered the nest and prevented entry by some females. Spawning involved repeated inversions by females and males releasing gametes on the ceiling of the nest. Males guarded the nest by blocking the entrance, producing agonistic vocalizations and chasing intruders. Inside the nest, eggs were regularly inspected by the males and constantly ventilated using pectoral and caudal fins. Up to three gravid females spawned sequentially in a nest. Peak ventilation occurred after egg deposition and declined with time until the parental male ate the eggs. The decline of parental care and egg cannibalism was likely an artifact of laboratory conditions and small brood size. Our findings offer new information on the reproductive habits of the invasive round goby. Because the reproductive sequence in the laboratory seems easy to disrupt, the procedures may lead to a management tool to control the spread of the species into new areas.     

加利福尼亚州的商业景观与购物环境

自20世纪中期第个郊区购物中心兴起之后．北美的商业景观设计也开始逐渐走向成熟。当时的创新理念是打造一个可控制的、无机动车和犯罪行为、室外环境良好的安全购物形式。规模较小的零售点通常会设置在大型购物中心的两端，以吸引购物者。     

Age of onset of child maltreatment predicts long-term mental health outcomes.

The authors tested the hypothesis that children who are maltreated earlier in life are at greater risk for poor psychological functioning in adulthood than those maltreated later in life. Age of onset of maltreatment was assessed with 3 classifications: (a) continuous (ages 0-11 years); (b) dichotomous (early [ages 0-5 years] vs. later [ages 6-11 years]); and (c) developmental (infancy [ages 0-2 years], preschool [ages 3-5 years], early school age [ages 6-8 years], and school age [ages 9-11 years]). Individuals with documented cases of physical and sexual abuse and neglect prior to age 12 (N=496) were followed up and assessed in adulthood. Results indicated that an earlier onset of maltreatment, measured dichotomously and developmentally, predicted more symptoms of anxiety and depression in adulthood, while controlling for gender, race, current age, and other abuse reports. Later onset of maltreatment, measured continuously or developmentally, was predictive of more behavioral problems in adulthood. Implications for the assessment of maltreated children, the prevention of adult psychopathology, and the classification of age of maltreatment onset are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stress, reactivity, and immune function in healthy men.

Examined the effects of acute psychological stress on lymphocyte proliferation and circulating levels of interleukin-1 and -2. 20 healthy men were exposed to 2 viewings of a gruesome surgery film and were asked to recall details of the film twice during a 20-min period. These Ss were compared to a nonstress control group of 9 Ss. Lymphocyte proliferation to the mitogen concanavalin-A was decreased during and after exposure to the stressor when compared to the control group. This decrease was more pronounced in Ss exhibiting greater blood pressure reactivity while viewing the film than in Ss showing smaller blood pressure responses. None of the other immunological measures was significantly affected by the stressor. Cortisol was not correlated with lymphocyte responsiveness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)