Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status

Genes of the RAF family encode kinases that are regulated by Ras and mediate cellular responses to growth signals. Activating mutations in one RAF gene, BRAF, have been found in a high proportion of melanomas and in a small fraction of other cancers. Here we show that BRAF mutations in colorectal cancers occur only in tumours that do not carry mutations in a RAS gene known as KRAS, and that BRAF mutation is linked to the proficiency of these tumours in repairing mismatched bases in DNA. Our results not only provide genetic support for the idea that mutations in BRAF and KRAS exert equivalent effects in tumorigenesis, but also emphasize the role of repair processes in establishing the mutation spectra that underpin human cancer.     

Inactivation of hCDC4 can cause chromosomal instability

Aneuploidy, an abnormal chromosome number, has been recognized as a hallmark of human cancer for nearly a century; however, the mechanisms responsible for this abnormality have remained elusive. Here we report the identification of mutations in hCDC4 (also known as Fbw7 or Archipelago) in both human colorectal cancers and their precursor lesions. We show that genetic inactivation of hCDC4, by means of targeted disruption of the gene in karyotypically stable colorectal cancer cells, results in a striking phenotype associated with micronuclei and chromosomal instability. This phenotype can be traced to a defect in the execution of metaphase and subsequent transmission of chromosomes, and is dependent on cyclin E--a protein that is regulated by hCDC4 (refs 2-4). Our data suggest that chromosomal instability is caused by specific genetic alterations in a large fraction of human cancers and can occur before malignant conversion.     

The Vision Conference: Facilitating Creative Processes

This paper presents the principles behind the design and management of the Vision Conference: a one-day workshop in which a large group of participants meet to create ideas, projects, and visions for the future activities of a local community or an organization. A case study from a local community in Denmark is also presented to illustrate the organization, planning, and management of a Vision Conference. The paper focuses on the three central social processes of the conference: group work, problem solving, and facilitation. The paper ends with a discussion of creativity and creativity techniques suitable for Vision Conferences.     

Full time adult credential students' instructional preferences at California State University, Long Beach: pedagogy orandragogy?

This study investigated the instructional preferences of full time adult credential students after they took a live course called Principles of Adult Education at California State University, Long Beach (CSULB) in the fall semester of 2002. These full time adult credential students had been working on their adult teaching credentials to meet the competencies specified by the California Commission on Teacher Credentialing. The course introduced students to Andragogy developed by Malcolm Knowles out of the andragogical model developed by Lindeman (1926). The study used Principles of Adult Learning Scales (PALS), advanced by Gary Conti in 1983 to measure instructional preferences. Data were collected from 30 (100% of 30) full time adult credential students enrolled in a live course to determine their instructional preferences of helping adults learn. The results of the study showed in most cases these adult learning professionals taught adult students andragogically; in some cases they taught adult students pedagogically.     

Genome shuffling leads to rapid phenotypic improvement in bacteria

For millennia, selective breeding, on the basis of biparental mating, has led to the successful improvement of plants and animals to meet societal needs. At a molecular level, DNA shuffling mimics, yet accelerates, evolutionary processes, and allows the breeding and improvement of individual genes and subgenomic DNA fragments. We describe here whole-genome shuffling; a process that combines the advantage of multi-parental crossing allowed by DNA shuffling with the recombination of entire genomes normally associated with conventional breeding. We show that recursive genomic recombination within a population of bacteria can efficiently generate combinatorial libraries of new strains. When applied to a population of phenotypically selected bacteria, many of these new strains show marked improvements in the selected phenotype. We demonstrate the use of this approach through the rapid improvement of tylosin production from Streptomyces fradiae. This approach has the potential to facilitate cell and metabolic engineering and provide a non-recombinant alternative to the rapid production of improved organisms.     

Future projections for Mexican faunas under global climate change scenarios

Global climates are changing rapidly, with unexpected consequences. Because elements of biodiversity respond intimately to climate as an important driving force of distributional limitation, distributional shifts and biodiversity losses are expected. Nevertheless, in spite of modelling efforts focused on single species or entire ecosystems, a few preliminary surveys of fauna-wide effects, and evidence of climate change-mediated shifts in several species, the likely effects of climate change on species' distributions remain little known, and fauna-wide or community-level effects are almost completely unexplored. Here, using a genetic algorithm and museum specimen occurrence data, we develop ecological niche models for 1,870 species occurring in Mexico and project them onto two climate surfaces modelled for 2055. Although extinctions and drastic range reductions are predicted to be relatively few, species turnover in some local communities is predicted to be high (>40% of species), suggesting that severe ecological perturbations may result.     

Rapidly recovering hydrogel scaffolds from self-assembling diblock copolypeptide amphiphiles

Protein-based hydrogels are used for many applications, ranging from food and cosmetic thickeners to support matrices for drug delivery and tissue replacement. These materials are usually prepared using proteins extracted from natural sources, which can give rise to inconsistent properties unsuitable for medical applications. Recent developments have utilized recombinant DNA methods to prepare artificial protein hydrogels with specific association mechanisms and responsiveness to various stimuli. Here we synthesize diblock copolypeptide amphiphiles containing charged and hydrophobic segments. Dilute solutions of these copolypeptides would be expected to form micelles; instead, they form hydrogels that retain their mechanical strength up to temperatures of about 90 degrees C and recover rapidly after stress. The use of synthetic materials permits adjustment of copolymer chain length and composition, which we varied to study their effect on hydrogel formation and properties. We find that gelation depends not only on the amphiphilic nature of the polypeptides, but also on chain conformations--alpha-helix, beta-strand or random coil. Indeed, shape-specific supramolecular assembly is integral to the gelation process, and provides a new class of peptide-based hydrogels with potential for applications in biotechnology.     

中文文本压缩的LZW算法

本文报告两个关于中文信息处理研究的结果:(1)采用Cover的方法,猜估中文信息熵,实验表明,中文信良熵不大于4.1bits/字。(2)根据中文的结构特性,选择Welch型的Lemple-Ziv数据压缩算法,把它移植、扩展于中文文本压缩上。应用该算法于不同类型的中文文本,本文获得一些中文文本压缩实际性能值。     

纤维素纳米晶对胶凝复合材料耐酸性能的影响

Acid mine drainage presents an important threat to cementitious structures. This study is aimed at investigating the effect of cellulose nanocrystals (CNCs) on the acid resistance of cementitious composites. CNCs were added to mortar mixtures as additives at cement volume ratios of 0.2vol%, 0.4vol%, 1.0vol%, and 1.5vol%. After 28 d of standard curing, the samples were immersed in a sulfuric acid with a pH value of 2 for 75 d. The unconfined compressive strength (UCS) test, the density, water absorption, void volume test, and thermogravimetric analysis were carried out to investigate the properties of CNC mixtures before sulfuric acid immersion. It was found that the addition of CNC reduced the volume of permeable voids and increased the hydration degree and mechanical strength of the samples. Changes in mass and length were monitored during immersion to evaluate the acid resistance of mixtures. The mixture with 0.4vol% CNC showed a reduced mass change and length change indicating its improved acid resistance.