Efficient generation of a reshaped human mAb specific for the {alpha} toxin of Clostridium perfringens

We have used the technique of antibody reshaping to producea humanized antibody specific for the a toxin of Clostridiumperfringens. The starting antibody was from a mouse hybridomafrom which variable (V) region nucleo-tide sequences were determined.The complementarity-determining regions (CDRs) from these Vregions were then inserted into human heavy and light chainV region genes with human constant region gene fragments subsequentlyadded. The insertion of CDRs alone into human frameworks didnot produce a functional reshaped antibody and modificationsto the V region framework were required. With minor frameworkmodifications, the affinity of the original murine mAb was restoredand even exceeded. Where affinity was increased, an alteredbinding profile to overlapping peptides was observed. Computermodelling of the reshaped heavy chain V regions suggested thatamino acids adjacent to CDRs can either contribute to, or distort,CDR loop conformation and must be adjusted to achieve high bindingaffinity.     

Treatment with alendronate prevents fractures in women at highest risk: results from the Fracture Intervention Trial

BACKGROUND: The efficacy of antiresorptive therapy in preventing fractures in women at highest fracture risk, such as very elderly women or those with severe osteoporosis, is uncertain. PARTICIPANTS AND METHODS: Using data from a double-blind, randomized, placebo-controlled clinical trial that enrolled 2027 postmenopausal women aged 55 to 81 years with low femoral neck bone mineral density (BMD) and existing vertebral fractures, we examined the consistency of the effect of treatment with alendronate sodium in preventing fractures within a priori-specified risk subgroups defined at baseline by age, bone density, number of preexisting vertebral fractures, and history of postmenopausal fracture. The women were randomized to oral administration of alendronate or placebo and followed up for an average of 2.9 years. The initial dose of alendronate sodium was 5 mg/d; the dosage was increased from 5 to 10 mg/d at 24 months. New vertebral fractures, the primary end point of this arm of the trial, were defined by morphometry as a decrease of 20% and at least 4 mm in any vertebral height between baseline and a follow-up radiograph at 36 months. Incident clinical fractures, the secondary end point, included nonspine and clinical (symptomatic) vertebral fractures. All clinical fractures were confirmed with x-ray film reports or, in the case of clinical vertebral fractures, x-ray films. RESULTS: Overall, there was a 47% significant reduction in risk of new vertebral fractures in the alendronate group compared with the placebo group. The reduction in risk of new vertebral fracture was consistent across fracture risk categories including age (relative risk [RR], 0.49 in women < 75 years compared with 0.62 in those > or = 75 years), BMD (RR, 0.54 in women with a femoral neck BMD < 0.59 g/cm2 [median] compared with 0.53 in those with a BMD > or = 0.59 g/cm2), and number of preexisting vertebral fractures (RR, 0.58 in women with 1 vertebral fracture compared with 0.52 in those with > or = 2). The overall significant 28% reduction in risk of incident clinical fractures in the alendronate group compared with the placebo group was also observed within these subgroups. Compared with the number of lower-risk women, a similar or smaller number of high-risk women needed to be treated to prevent 1 fracture. For example, 8 women aged 75 years or older compared with 9 women younger than 75 years, or 4 women with 2 or more existing vertebral fractures compared with 16 women with 1 existing vertebral fracture, needed to be treated with alendronate for 5 years to prevent 1 new vertebral fracture. CONCLUSIONS: Alendronate effectively reduces fracture risk in postmenopausal women with vertebral fractures and low BMD, including those women at highest risk because of advanced age or severe osteoporosis. Since the risk reductions observed with alendronate treatment were consistent within fracture risk categories, more fractures were prevented by treating women at highest risk.     

Flexible speech translation systems

Speech translation research has made significant progress over the years with many high-visibility efforts showing that translation of spontaneously spoken speech from and to diverse languages is possible and applicable in a variety of domains. As language and domains continue to expand, practical concerns such as portability and reconfigurability of speech come into play: system maintenance becomes a key issue and data is never sufficient to cover the changing domains over varying languages. In this paper, we discuss strategies to overcome the limits of today's speech translation systems. In the first part, we describe our layered system architecture that allows for easy component integration, resource sharing across components, comparison of alternative approaches, and the migration toward hybrid desktop/PDA or stand-alone PDA systems. In the second part, we show how flexibility and reconfigurability is implemented by more radically relying on learning approaches and use our English-Thai two-way speech translation system as a concrete example.     

Ampacities of power cables wound on reels

This paper presents a mathematical model that is capable of calculating the ampacity of a wide variety of power cable designs consisting of an arbitrary number of layers on a cable reel. The model considers round cables with copper conductors. The validity and accuracy of the ampacity model were verified by comparing the predicted temperature distribution within the reel with measured temperatures collected during an extensive testing program conducted at the US Bureau of Mines (USBM). The mathematical model predicted a temperature distribution within the cable layers that was very close to the measured variation in temperature. The value of the program is illustrated by calculating ampacities for several copper conductor sizes     

Reduction of residual stress in montmorillonite/epoxy compounds

An epoxy resin was cured while in intimate contact with small amounts of epoxyphilic montmorillonites. It was determined that cured epoxy exists within the montmorillonite interlayer by the observation of very high interlayer spacings, even greater than 8 nm, Generally, epoxy compounds containing montmorillonites that had been swollen in the curing agent prior to curing exhibited larger interlayer spacings, especially among the non-dispersed montmorillonite layers. The maximum observed residual stress was reduced by greater than 50% in the epoxyphilic montmorillonite/epoxy compounds over that of the pure epoxy. The epoxyphilic montmorillonite/epoxy compounds generally exhibited higher values of glass transition temperature, flexural modulus, and ultimate flexural strength than the pure epoxy. The tyramine-montmorillonite compounds typically had the highest values overall.     

The dieting maelstrom: Is it possible and advisable to lose weight?

An impassioned debate over the virtues and dangers of dieting is polarizing the field and diverts attention from key issues. Dieting clearly has costs and, for some, has the potential for benefit. The primary challenges are (1) to identify individuals who will be helped or harmed by dieting, (2) to reduce the frequency and severity of dieting in those for whom the costs exceed the benefits, (3) to better understand the physiological and psychological reasons why some people can lose and others cannot, and (4) to develop safe and effective means for weight loss and its maintenance and to target these methods to individuals who stand to benefit. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of not breastfeeding on the risk of diarrheal and respiratory mortality in children under 2 years of age in Metro Cebu, The Philippines

The effects of not breastfeeding on mortality due to diarrhea and acute lower respiratory infection (ALRI) in children under 2 years of age were examined using data from a 1988-1991 longitudinal study of 9,942 children in Metro Cebu, The Philippines. Cox regression methods were used to study the magnitude of the risks, possible interactions with birth weight and nutritional status, and the effect of additional confounding factors. Not breastfeeding had a greater effect on diarrheal mortality than on ALRI mortality. In the first 6 months of life, failing to initiate breastfeeding or ceasing to breastfeed resulted in an 8- to 10-fold increase in the rate of diarrheal mortality. The rate of mortality associated with both ALRI and diarrhea was increased nearly six times by not breastfeeding, but the rate of ALRI mortality alone was not increased. The data also suggested that the risk of mortality associated with not breastfeeding was greater for low birth weight infants and infants whose mothers had little formal education. After age 6 months, the protective effects of breastfeeding dropped dramatically. These findings underscore the importance of promoting breastfeeding, especially during the first 6 months of life, and of targeting high risk groups such as low birth weight babies and those of low socioeconomic status.     

Effect of pretreatments and freezing rate on the firmness of potato tissue after a freeze–thaw cycle

The texture of potato tissue after a freeze–thaw process using different freezing rates and different pretreatments was analysed, in order to select the best strategy for optimum preservation of the textural characteristics of pre‐frozen potato. Ten blanching conditions were tested and a two‐step blanching process with calcium chloride (0.07 g mL^?1) proved the most effective in protecting the tissue after a freeze–thaw process (maximum load force around 10–55% of the raw tissue, depending on potato batch, for air‐blast freezing and 20–60% for immersion freezing). Vacuum impregnation at 100 and 400 mbar, even when followed by different pre‐drying treatments to remove excess water, was very detrimental to resistance to a freeze–thaw process (maximum load force below 10% of the raw tissue for air‐blast freezing and below 20% for immersion freezing). Microstructure analysis confirmed better tissue integrity retention with ethyleneglycol immersion freezing instead of air‐freezing. Differences were found between batches with a 6‐month difference in storage time, indicating that the fresher batch was more suitable for freezing.     

Block Copolymer Surface Reconstuction: A Reversible Route to Nanoporous Films

Thin films of block copolymers have been used as templates and scaffolds for the fabrication of arrays of nanostructured materials. In general, a chemical modification of the film or the removal of one of the components by photodegradative methods is required to produce a nanoporous film that serves as a template or scaffold. Here, however, the preferential interaction of one of the components with a solvent is shown to produce a reconstruction of the block copolymer film that, upon drying, leads to the generation of a nanoporous template. The area density of the pores is identical to that of the original copolymer thin film. Since no chemical reactions occurr, the process is fully reversible. Upon heating the copolymer film above its glass‐transition temperature, mobility is imparted to the copolymer and the original copolymer film with oriented domains is recovered. The film reconstruction significantly simplifies the generation of nanoporous templates.