The evolution of custom microarray manufacture

Given the enormous size of the genome and that there are potentially many other types of measurements we need to do to understand it, it has become necessary to pick and choose one's targets to measure because it is still impossible to evaluate the entire genome all at once. What has emerged is a need to have rapidly customizable microarrays. There are two dominant methods to accomplish custom microarray synthesis, Affymetrix-like microarrays manufactured using light projection rather than semiconductor-like masks used by Affymetrix to mass manufacture their GeneChip/sup TM/ arrays now, or the ink-jet printing method employed by Agilent. The manufacture of these custom Affymetrix-like microarrays can now be done on a digital optical chemistry (DOC) machine developed at the University of Texas Southwestern Medical Center, and this method offers much higher feature numbers and feature density than is possible with ink-jet printed arrays. On a microarray, each feature contains a single genetic measurement. The initial DOC prototype has been described in several publications, but that has now led to a second-generation machine. This machine reliably produces a number of arrays daily, has been deployed against a number of biomedical questions, is being used in new ways and has also led to a number of spin-off technologies.     

Menadione-induced oxidative stress accelerates onset of Emory mouse cataract in vivo

This article takes issue with procedural reductionism, which is the inclination to reduce all matters of judgement and responsibility to the following of some procedure or rule. Two scenarios provide content for a discussion of professional discretion in the context of accountability. The author shows that in professional life there will always be situations that stand beyond the rules of procedures and require the unique judgement of the professional at the time. While this judgement may be determined by the facts available in a situation of uncertainty, it cannot be reduced to the facts (including facts about rules and procedures). The moral judgement will still have an essential indeterminancy about it.     

Recovery of SDS-protein and DNA using commercial automated gel electrophoresis apparatus

Forty-seven children afflicted with acute leukemia were studied at the Tata Memorial Hospital Bombay to record the occurrence of oral manifestations prior to and during chemotherapy. Lymphadenopathy was the most frequent single finding suggestive of leukemia during head and neck examination. Gingival abnormalities, bleeding gums and oral mucosal pallor were the other findings on initial oral examination. Due to immunosuppression caused by the chemotherapy drugs oral mucosal ulcerations, uncontrolled herpes, candidiasis and pseudomoniasis were observed.     

Clinical trial of ototopical ofloxacin for treatment of chronic suppurative otitis media

A multicenter, open-label prospective trial was performed to determine the clinical and microbiologic efficacy of ofloxacin (OFLX) otic solution in the treatment of subjects > or =12 years with chronic suppurative otitis media (CSOM) and a chronically perforated tympanic membrane in the infected ear(s). A total of 207 patients at 27 centers in the United States and Central America received OFLX 0.5 mL instilled ototopically twice daily for 14 consecutive days. The primary clinical end point was cure (dry ear) or failure (not dry ear). The primary microbiologic end point was eradication of baseline pathogens. Because there was no comparator and there were few data in the literature regarding clinical efficacy in patients treated with other regimens, the efficacy of OFLX was compared with data recorded in the clinical records of historical-practice control (HPC) or current-practice control (CPC) subjects. The incidence of clinical cure in clinically evaluable OFLX-treated patients (91%; 148 of 162 subjects) was significantly higher than in HPC subjects (67%; 124 of 185 subjects) or CPC subjects (70%; 38 of 54 subjects). OFLX eradicated all baseline pathogens isolated in microbiologically evaluable subjects. These pathogens were predominantly Staphylococcus aureus, Pseudomonas aeruginosa, and Proteus mirabilis. The most common treatment-related adverse event, bitter taste, occurred in 17% (35 of 207) of OFLX-treated subjects. Thus OFLX 0.5 mL administered twice daily for 14 days was effective in resolving the signs and symptoms of CSOM in subjects > or =12 years, was significantly more effective than therapies used to treat HPC or CPC subjects, and was well tolerated.     

Animal model for the study of methanol toxicity: comparison of folate-reduced rat responses with published monkey data

The postpartum period is an ideal time to begin contraception, as women are more highly motivated to adopt contraception at this time and it is convenient for both patients and service providers. For intrauterine device (IUD) contraception, this period offers other advantages, such as ease of insertion and minimal adverse impacts on breastfeeding. Among early studies, most postpartum insertions were performed anywhere from a few hours to seven days or more after delivery, and retention of the IUD in the uterus was poor. Since the 1970s, immediate postplacental insertion (IPPI), i.e., IUD insertion performed within 10 minutes after placental delivery, has been advocated, and fairly, low expulsion rates have been reported. Up to now, IPPI has not been widely accepted in clinics because its expulsion rate still appears to be higher than that of interval insertion. In order to further study IPPI and perfect this contraceptive technique, it is essential to comprehensively review IPPI results and compare the Chinese experience with that of the rest of the world.     

The effect of composition on the properties of nylon 612 copolymers

The series of nylon 612 copolymers was synthesized from caprolactam (C) and laurolactam (L) at 145°C. The 50/50 C/L molar ratio copolymer was found to have the minimum melting temperature (T_m ) for the series. The glass transition temperatures (T_g 's) of the copolymers were affected by the crystallinity of the copolymers. The T_g was at a minimum for the 50/50 copolymer for crystalline samples. However, for amorphous samples there was a decrease in T_g with increasing L content. Percent crystallinity was determined by differential scanning calorimetry and X-ray techniques. It was found that the degree of crystallinity was at a minimum for copolymers of 70/30 to 40/60 C/L ratios. Coefficients of linear thermal expansion (CLTE) were obtained for the copolymers at 10°C intervals from 20 to 70°C for dry and from 20 to 50°C for samples conditioned at 50% relative humidity and 50°C. The dry samples gave lower initial values, but had a greater temperature dependence than the conditioned samples. As expected, the CLTE was found to be lowest for samples exhibiting the highest crystallinity. The tensile strengths and moduli decreased rapidly with increasing L up to the 70/30 C/L ratio after which they remained relatively constant. Elongations reached maximums between 70/30 and 40/60 C/L ratios. An inverse relationship was found between crystallinity and impact strength.     

Learning from designing the RoboFesta—Blue Peter robots

Can children and adults learn anything from building robots? In 2001 we ran a robot design competition with the BBC TelevisionBlue Peter, program. Some 32 000 children, aged between 5 and 16 years, submitted paper designs. We built prototypes of the four winners' robots for a Robot Design MasterClass at the London Science Museum. It is widely believed that across the curriculum, robotics is a powerful force in motivating education. We ask what the children learned from the robot design process. Our answer is that they learned many things, both inside and outside the science and technology curriculum.     

A Conditionally Fluorescent Peptide Reporter of Secondary Structure Modulation

Proteins containing intrinsic disorder often form secondary structure upon interaction with a binding partner. Modulating such structures presents an approach for manipulating the resultant functional outcomes. Translational repressor protein 4E-BP1 is an example of an intrinsically disordered protein that forms an α-helix upon binding to its protein ligand, eIF4E. Current biophysical methods for analyzing binding-induced structural changes are low-throughput, require large amounts of sample, or are extremely sensitive to signal interference by the ligand itself. Herein, we describe the discovery and development of a conditionally fluorescent 4E-BP1 peptide that reports structural changes of its helix in high-throughput format. This reporter peptide is based on conditional quenching of fluorescein by thioamides. In this case, fluorescence signal increases as the peptide becomes more ordered. Conversely, destabilization of the α-helix results in decreased fluorescence signal. The low concentration and low volume of peptide required make this approach amenable for high-throughput screening to discover ligands that alter peptide secondary structure.