Home About us Contact
|
Home About us Contact | ||
|
|
||
Screening Process (screening + process)
Selected AbstractsInvestigation of prolonged neonatal jaundiceACTA PAEDIATRICA, Issue 6 2000S Hannam Jaundice persisting beyond 14 d of age (prolonged jaundice) can be a sign of serious underlying liver disease. Protocols for investigating prolonged jaundice vary in complexity and the yield from screening has not been assessed. In order to address these issues, we carried out a prospective study of term infants referred to our neonatal unit with prolonged jaundice over an 18 mo period. Infants were examined by a paediatrician and had the following investigations: a total and conjugated serum bilirubin, liver function tests, full blood count, packed cell volume, group and Coombs' test, thyroid function tests, glucose-6-phosphate dehydrogenase levels and urine for culture. One-hundred-and-fifty-four infants were referred with prolonged jaundice out of 7139 live births during the study period. Nine infants were referred to other paediatric specialties. One infant had a conjugated hyperbilirubinaemia, giving an incidence of conjugated hyperbilirubinaemia of 0.14 per 1000 live births. Diagnoses included: giant cell hepatitis (n= 1), hepatoblastoma (n= 1), trisomy 9p (n= 1), urinary tract infections (n= 2), glucose-6-phosphate dehydrogenase deficiency (n= 3) and failure to regain birthweight (n= 1). Conclusions: In conclusion, a large number of infants referred to hospital for prolonged jaundice screening had detectable problems. The number of investigations may safely be reduced to: a total and conjugated bilirubin, packed cell volume, glucose-6-phosphate dehydrogenase level (where appropriate), a urine for culture and inspection of a recent stool sample for bile pigmentation. Clinical examination by a paediatrician has a vital role in the screening process. [source] Screening for dyslexia, dyspraxia and Meares-Irlen syndrome in higher educationDYSLEXIA, Issue 1 2009S. A. Nichols Abstract This study reports a comparison of screening tests for dyslexia, dyspraxia and Meares-Irlen (M-I) syndrome in a Higher Education setting, the University of Worcester. Using a sample of 74 volunteer students, we compared the current tutor-delivered battery of 15 subtests with a computerized test, the Lucid Adult Dyslexia Screening test (LADS), and both of these with data on assessment outcomes. The sensitivity of this tutor battery was higher than LADS in predicting dyslexia, dyspraxia or M-I syndrome (91% compared with 66%) and its specificity was lower (79% compared with 90%). Stepwise logistic regression on these tests was used to identify a better performing subset of tests, when combined with a change in practice for M-I syndrome screening. This syndrome itself proved to be a powerful discriminator for dyslexia and/or dyspraxia, and we therefore recommend it as the first stage in a two-stage screening process. The specificity and sensitivity of the new battery, the second part of which comprises LADS plus four of the original tutor delivered subtests, provided the best overall performance: 94% sensitivity and 92% specificity. We anticipate that the new two-part screening process would not take longer to complete. Copyright © 2008 John Wiley & Sons, Ltd. [source] Screening for fetal alcohol syndrome: is it feasible and necessary?ADDICTION BIOLOGY, Issue 2 2000Larry Burd The potential to utilize screening strategies to improve the identification and outcome of persons with fetal alcohol syndrome (FAS) is reviewed. FAS is a condition where screening and surveillance activities would be appropriate. Development of FAS screening and surveillance programs is encouraged because the disorder is expensive. People with FAS have poor outcomes as adults with less than 10% living independently. Several useful tools and models are available. Screening would improve ascertainment and prevalence estimates. Early identification could improve access to services and long term outcome, secondary disabilities and, by extension, excess disability in affected children could be decreased. Lastly, mothers who are at the highest risk to have additional children with FAS could be identified and offered treatment. While both screening and surveillance activities are discussed, the principle focus of this article is a review of the screening process. Two screening tools and several screening methodologies for FAS are available. Since no test will be appropriate in all settings, screening tests need to be selected depending on the setting and population of interest. Screening for FAS should be conducted in a variety of settings and in populations of both high and moderate risk. The results would also provide important data to influence public policy development and resource allocation. Appropriate evaluation of the efficacy, efficiency and effectiveness of FAS screening tools and methodologies would be important before utilization in screening programs. [source] Germline mutations of BRCA1 and BRCA2 in Korean breast and/or ovarian cancer families,,HUMAN MUTATION, Issue 3 2002Hio Chung Kang Abstract Germline mutations in the BRCA1 and BRCA2 genes are responsible for the predisposition and development of familial breast and/or ovarian cancer. Most mutations of BRCA1 and BRCA2 associated with breast and/or ovarian cancer result in truncated proteins. To investigate the presence of BRCA1 and BRCA2 germline mutations in Korean breast and/or ovarian cancer families, we screened a total of 27 cases from 21 families including two or more affected first- or second-degree relatives with breast and/or ovarian cancer. PTT, PCR-SSCP, and DHPLC analysis, followed by sequencing were used in the screening process. In nine families, we found BRCA1 and BRCA2 germline mutations that comprised four frameshift mutations and five nonsense mutations. All nine mutations led to premature termination producing shortened proteins. Among the nine mutations, three novel BRCA1 mutations (E1114X, Q1299X, 4159delGA) and two novel BRCA2 mutations (K467X, 8945delAA) were identified in this work. © 2002 Wiley-Liss, Inc. [source] Screening for depression and anxiety: correlates of non-response and cohort attrition in the Netherlands Study of Depression and Anxiety (NESDA)INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 4 2009Willem Jan Van Der Veen Abstract A major problem in the analysis of attrition of cohorts in studies on mental health problems is that data on those who do not participate at the outset of a study are largely unavailable. It is not known how underlying psychopathology affects the first stages of screening where non-response and selectivity are usually highest. This article presents results of one of the centres of the Netherlands Study of Depression and Anxiety (NESDA), a longitudinal study aimed at describing the long-term course and consequences of depression and anxiety disorders. The aim is to describe the different ways of attrition during the first NESDA-wave in a cohort of patients aged 18,65 years of the Registration Network Groningen and to analyse whether attrition is related to gender, age and psychopathology as recorded in general practice. The attrition of the study cohort (n = 8475) was highest during the first stages, eventually leading to a population of 169 patients only who participated in the full NESDA-programme. Probabilities of transition from one stage of the screening process to the next were regressed on selected background variables using binary logistic regression. Correlates of participation were being female and being older (>40). Psychopathology was an important variable in the formation of the initial sample cohort, but only had a weak influence on patient response to the screening questionnaire. Study design factors had a stronger impact on the changing composition of the cohort at each screening stage compared to patient factors. Copyright © 2009 John Wiley & Sons, Ltd. [source] [Fe-Fe]-hydrogenase reactivated by residue mutations as bridging carbonyl rearranges: A QM/MM studyINTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 14 2010Stefan Motiu Abstract In this work, we found aqueous enzyme phase reaction pathways for the reactivation of the exogenously inhibited [Fe-Fe]-hydrogenases by O2, or OH,, which metabolizes to H2O (Dogaru et al., Int J Quantum Chem 2008, 108; Motiu et al., Int J Quantum Chem 2007, 107, 1248). We used the hybrid quantum mechanics/molecular mechanics (QM/MM) method to study the reactivation pathways of the exogenously inhibited enzyme matrix. The ONIOM calculations performed on the enzyme agree with experimental results (Liu et al., J Am Chem Soc 2002, 124, 5175), that is, wild-type [Fe-Fe]-hydrogenase H-cluster is inhibited by oxygen metabolites. An enzyme spherical region with a radius of 8 Å (from the distal iron, Fed) has been screened for residues that prevent H2O from leaving the catalytic site and reactivate the [Fe-Fe]-hydrogenase H-cluster. In the screening process, polar residues were removed, one at a time, and frequency calculations provided the change in the Gibbs' energy for the dissociation of water (due to their deletion). When residue deletion resulted in significant Gibbs' energy decrease, further residue substitutions have been carried out. Following each substitution, geometry optimization and frequency calculations have been performed to assess the change in the Gibbs' energy for the elimination of H2O. Favorable thermodynamic results have been obtained for both single residue removal (,G,Glu374 = ,1.6 kcal/mol), single substitution (,GGlu374His = ,3.1 kcal/mol), and combined residue substitutions (,GArg111Glu;Thr145Val;Glu374His;Tyr375Phe = ,7.5 kcal/mol). Because the wild-type enzyme has only an endergonic step to overcome, that is, for H2O removal, by eliminating several residues, one at a time, the endergonic step was made to proceed spontaneously. Thus, the most promising residue deletions which enhance H2O elimination are ,Arg111, ,Thr145, ,Ser177, ,Glu240, ,Glu374, and ,Tyr375. The thermodynamics and electronic structure analyses show that the bridging carbonyl (COb) of the H-cluster plays a concomitant role in the enzyme inhibition/reactivation. In gas phase, COb shifts towards Fed to compensate for the electron density donated to oxygen upon the elimination of H2O. However, this is not possible in the wild-type enzyme because the protein matrix hinders the displacement of COb towards Fed, which leads to enzyme inhibition. Nevertheless, enzyme reactivation can be achieved by means of appropriate amino acid substitutions. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010 [source] Directed Evolution of an Enantioselective Enoate-Reductase: Testing the Utility of Iterative Saturation MutagenesisADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 18 2009Despina Abstract Directed evolution utilizing iterative saturation mutagenesis (ISM) has been applied to the old yellow enzyme homologue YqjM in the quest to broaden its substrate scope, while controlling the enantioselectivity in the bioreduction of a set of substituted cyclopentenone and cyclohexenone derivatives. Guided by the known crystal structure of YqjM, 20 residues were selected as sites for saturation mutagenesis, a pooling strategy based on the method of Phizicky [M. R. Martzen, S. M. McCraith, S. L. Spinelli, F. M. Torres, S. Fields, E. J. Grayhack, E. M. Phizicky, Science1999, 286, 1153,1155] being used in the GC screening process. The genes of some of the hits were subsequently employed as templates for randomization experiments at the other putative hot spots. Both (R)- and (S)-selective variants were evolved using 3-methylcyclohexenone as the model substrate in the asymmetric bioreduction of the olefinic functionality, only small mutant libraries and thus minimal screening effort being necessary. Some of the best mutants also proved to be excellent catalysts when testing other prochiral substrates without resorting to additional mutagenesis/screening experiments. Thus, the results constitute an important step forward in generalizing the utility of ISM as an efficient method in laboratory evolution of enzymes as catalysts in organic chemistry. [source] How Can We Improve the Accuracy of Screening Instruments?LEARNING DISABILITIES RESEARCH & PRACTICE, Issue 4 2009Evelyn S. Johnson Screening for early reading problems is a critical step in early intervention and prevention of later reading difficulties. Evaluative frameworks for determining the utility of a screening process are presented in the literature but have not been applied to many screening measures currently in use in numerous schools across the nation. In this study, the accuracy of several Dynamic Indicators of Basic Early Literacy Skills (DIBELS) subtests in predicting which students were at risk for reading failure in first grade was examined in a sample of 12,055 students in Florida. Findings indicate that the DIBELS Nonsense Word Fluency, Initial Sound Fluency, and Phoneme Segmentation Fluency measures show poor diagnostic utility in predicting end of Grade 1 reading performance. DIBELS Oral Reading Fluency in fall of Grade 1 had higher classification accuracy than other DIBELS measures, but when compared to the classification accuracy obtained by assuming that no student had a disability, suggests the need to reevaluate the use of classification accuracy as a way to evaluate screening measures without discussion of base rates. Additionally, when cut scores on the screening tools were set to capture 90 percent of all students at risk for reading problems, a high number of false positives were identified. Finally, different cut scores were needed for different subgroups, such as English Language Learners. Implications for research and practice are discussed. [source] Combinatorial engineering to enhance thermostability of amylosucrasePROTEIN SCIENCE, Issue 6 2008Stéphane Emond Abstract Amylosucrase is a transglucosidase that catalyzes amylose-like polymer synthesis from sucrose substrate. About 60,000 amylosucrase variants from two libraries generated by the MutaGen random mutagenesis method were submitted to an in vivo selection procedure leading to the isolation of more than 7000 active variants. These clones were then screened for increased thermostability using an automated screening process. This experiment yielded three improved variants (two double mutants and one single mutant) showing 3.5- to 10-fold increased half-lives at 50°C compared to the wild-type enzyme. Structural analysis revealed that the main differences between wild-type amylosucrase and the most improved variant (R20C/A451T) might reside in the reorganization of salt bridges involving the surface residue R20 and the introduction of a hydrogen-bonding interaction between T451 of the B, domain and D488 of flexible loop 8. This double mutant is the most thermostable amylosucrase known to date and the only one usable at 50°C. At this temperature, amylose synthesis by this variant using high sucrose concentration (600 mM) led to the production of amylose chains twice as long as those obtained by the wild-type enzyme at 30°C. [source] Rapid selection of peptide containing fractions in off-line 2-D HPLC in shotgun proteome analysis by screening with MALDI TOF MSPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 19 2009Maria Lasaosa A simple and fast screening method for the selection of fractions of first dimension separation to be analyzed in second dimension-MS/MS experiments in offline multidimensional liquid chromatographic separation schemes for shotgun proteome analysis was developed. The method is based on the measurement of total peptide content of the first dimension fractions by MALDI MS and was established using a tryptic digest of a bacterial proteome. The results of the screening process were in good agreement with those obtained in a detailed proteome analysis performed by RP×ion-pair RP-MALDI TOF/TOF MS analysis. The method supports a straightforward planning of experiments, also enabling a reduction of overall measurement time in shotgun proteome analysis. [source] Burnout, psychiatric morbidity, and work-related sources of stress in paediatric oncology staff: a review of the literaturePSYCHO-ONCOLOGY, Issue 10 2009Suzanne Mukherjee Abstract Objective: A growing body of research suggests that staff working in adult oncology services are at risk of burnout and psychiatric morbidity, but whether or not these findings can be generalised to staff working in paediatric oncology is questionable. This paper reports the findings of a comprehensive review of the literature on burnout, psychiatric morbidity, and sources of work-related stress in paediatric oncology staff. Methods: Electronic searches of MEDLINE and PSYCHINFO. This was followed by a screening process, during which papers where checked against inclusion and exclusion criteria, and the quality of study reporting was assessed. Information about the study design and methods was then extracted from each paper so that the methodological quality could be critiqued. Results: Ten studies meeting the review inclusion criteria were identified. No studies were identified which compared paediatric and adult oncology staff. Research on paediatric oncology staff has failed to use the well-established standardised measures of burnout and psychiatric morbidity employed in studies of adult oncology staff. There is some qualitative evidence to suggest paediatric oncology nurses experience a unique, additional set of stressors not encountered by colleagues in adult oncology services. Conclusion: The evidence on stress and burnout in paediatric oncology staff is extremely limited. In order to devise appropriate and effective interventions to support staff, we need to have a much better understanding of the level of burnout and psychiatric morbidity experienced by all members of the paediatric oncology multi-disciplinary team, as well as the factors that contribute to these experiences. Copyright © 2009 John Wiley & Sons, Ltd. [source] Reach out to ENhancE Wellness in Older Cancer Survivors (RENEW): design, methods and recruitment challenges of a home-based exercise and diet intervention to improve physical function among long-term survivors of breast, prostate, and colorectal cancer,PSYCHO-ONCOLOGY, Issue 4 2009Denise Clutter Snyder Abstract Objective: Cure rates for cancer are increasing, especially for breast, prostate, and colorectal cancer. Despite positive trends in survivorship, a cancer diagnosis can trigger accelerated functional decline that can threaten independence, reduce quality-of-life and increase healthcare costs, especially among the elderly who comprise the majority of survivors. Lifestyle interventions may hold promise in reorienting functional decline in older cancer survivors, but few studies have been conducted. Methods: We describe the design and methods of a randomized controlled trial, RENEW (Reach out to ENhancE Wellness), that tests whether a home-based multi-behavior intervention focused on exercise, and including a low saturated fat, plant-based diet, would improve physical functioning among 641 older, long-term (,5 years post-diagnosis) survivors of breast, prostate, or colorectal cancer. Challenges to recruitment are examined. Results: Twenty thousand and fifteen cases were approached, and screened using a two-step screening process to assure eligibility. This population of long-term, elderly cancer survivors had lower rates of response (,11%) and higher rates of ineligibility (,70%) than our previous intervention studies conducted on adults with newly diagnosed cancer. Significantly higher response rates were noted among survivors who were White, younger, and more proximal to diagnosis and breast cancer survivors (p -values<0.001). Conclusion: Older cancer survivors represent a vulnerable population for whom lifestyle interventions may hold promise. RENEW may provide guidance in allocating limited resources in order to maximize recruitment efforts aimed at this needy, but hard-to-reach population. Copyright © 2008 John Wiley & Sons, Ltd. [source] Outcomes and Efficacy of Newborn Hearing Screening: Strengths and Weaknesses (Success or Failure?),THE LARYNGOSCOPE, Issue 7 2008S. Korres MD Abstract Objective: To assess the outcomes of neonatal hearing screening with regard to the final diagnosis in a very large number of newborns and investigate related strengths and weaknesses of the program. Subjects: In this study, 76,560 newborns were assessed. Method: All neonates were assessed using transient evoked otoacoustic emissions (TEOAEs). Results: From the 76,560 neonates screened, 1,564 (2%) failed the test. According to the screening protocol, all parents of failed neonates were asked to bring their children 1 month following discharge to repeat the test. Of the 541 (34.6%) newborns who repeated the test, 303 (56%) were found normal and 238 (44%) again failed TEOAE. The latter children were referred to two special public centers for full audiology evaluation. In addition, 124 neonates were also referred due to other reasons revealed in the screening process (family history, high levels of bilirubin, etc.). Of the 362 children who were referred to the two special audiology centers, 113 (31.2%) were evaluated by these two centers. In addition, 42 children who had failed initial screening and did not show up for a follow-up appointment to repeat TEOAE were also assessed in the same centers. Of the 155 children who had a special audiologic evaluation, 56 (36.1%) were found to have hearing loss (HL) and 99 (63.9%) normal hearing. In detail, 28 had bilateral sensorineural HL greater than 40 dB, 10 had unilateral sensorineural HL greater than 40 dB, and 18 had otitis media with effusion or other conductive HL. Conclusions: Derived from the present study: 1) repeated testing of "failed" newborns in the maternity hospital and before discharge leads to an acceptable referral rate of 2%; 2) the 1-month follow-up of "failed" newborns further limits the false positive results but leads to high rate of newborns lost to follow-up; 3) a dedicated secretariat system should be implemented to follow-up each "failed" newborn and remind parents about their follow-up appointments; and 4) additional measures such as detailed educational material and parental friendly approach should also be implemented. [source] On increasing protein-crystallization throughput for X-ray diffraction studiesACTA CRYSTALLOGRAPHICA SECTION D, Issue 2 2005Ashit K. Shah Two recent developments, a novel screening/optimization strategy that considerably reduces the number of trials required to produce diffraction-size crystals and a simple modification that doubles the screening capacity of the Douglas Instruments ORYX 1-6 protein-crystallization robot, have been implemented into a structural genomics project. The new two-step screening/optimization strategy yields diffraction-quality crystals directly from the screening process, reducing the need for further optimization. The ORYX modification involves the addition of extensions to the sample- and oil-delivery arms and software modifications that allow two plates to be set up simultaneously. [source] The state of residential care for people with mental illness; insights from an audit of the screening tool for entry to licensed residential facilitiesAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 2 2009Lauren J. Bailey Abstract Objective: To describe the medical and psychiatric profile of people assessed with the ,Screening Tool for Entry to Licensed Residential Centres' (Boarding House Screening Tool), examine the impact on their accommodation and the screening process. Methods: Copies of all of the Boarding House Screening Tools completed by the Camperdown Aged Care Assessment Team in 2003 and 2004 were examined. Accommodation status in 2006 was obtained from the Boarding House Team, GP or hospital database. A structured telephone survey of Aged Care Assessment Team staff was performed. Results: Thirty-nine Boarding House Screening Tools were reviewed. The mean age of the screened population was 43 yrs (range 22-76 yrs), most were men (36M: 3F). Eighty-two per cent had a listed psychiatric diagnosis, 23% a recent history of substance abuse, 10% a diagnosis of intellectual disability/cognitive impairment and 28% had more than two listed medical diagnoses. Seven people (18%), diagnosed with Schizophrenia, were not approved by the Boarding House Screening Tool because of high care needs and/or violent behaviour, however, only one remained in a high care facility in 2006. Forty-two per cent of people approved by the Boarding House Screening Tool were living in Licensed Boarding Houses in 2006. Conclusion and implications: People being assessed for entry to Licensed Boarding Houses are young with high levels of psychiatric illness, medical co-morbidity and drug and alcohol use. The Boarding House Screening Tool is effective in keeping people who are not approved out of Licensed Boarding Houses; however, even if approved this accommodation is short-term in the majority of cases. [source] Evaluation of a mobile screening service for abdominal aortic aneurysm in Broken Hill, a remote regional centre in far western NSWAUSTRALIAN JOURNAL OF RURAL HEALTH, Issue 2 2010Margaret S. Lesjak Abstract Objectives:,To evaluate the feasibility of a mobile screening service model for abdominal aortic aneurysm (AAA) in a remote population centre in Australia. Design:,Screening test evaluation. Setting:,A remote regional centre (population: 20 000) in far western NSW. Participants:,Men aged 65,74 years, identified from the Australian Electoral roll. Interventions:,A mobile screening service using directed ultrasonography, a basic health check and post-screening consultation. Main outcome measures:,Attendance at the screening program, occurrence of AAA in the target population and effectiveness of screening processes. Results:,A total of 516 men without a previous diagnosis of AAA were screened, an estimated response rate of 60%. Of these, 463 (89.7%) had a normal aortic diameter, 28 (5.4%) ectatic and 25 (4.9%) a small, moderate or significant aneurysm. Two men with AAA were recommended for surgery. Feedback from participants indicated that the use of a personalised letter of invitation helped with recruitment, that the screening process was acceptable and the service valued. Conclusions:,It is feasible to organise and operate a mobile AAA screening service from moderate sized rural and remote population centres. This model could be scaled up to provide national coverage for rural and remote residents. [source] Bayesian Optimal Design for Phase II Screening TrialsBIOMETRICS, Issue 3 2008Meichun Ding Summary Most phase II screening designs available in the literature consider one treatment at a time. Each study is considered in isolation. We propose a more systematic decision-making approach to the phase II screening process. The sequential design allows for more efficiency and greater learning about treatments. The approach incorporates a Bayesian hierarchical model that allows combining information across several related studies in a formal way and improves estimation in small data sets by borrowing strength from other treatments. The design incorporates a utility function that includes sampling costs and possible future payoff. Computer simulations show that this method has high probability of discarding treatments with low success rates and moving treatments with high success rates to phase III trial. [source] Addressing the Numbers Problem in Directed EvolutionCHEMBIOCHEM, Issue 11 2008Manfred T. Reetz Prof. Dr. Abstract Our previous contribution to increasing the efficiency of directed evolution is iterative saturation mutagenesis (ISM) as a systematic means of generating focused libraries for the control of substrate acceptance, enantioselectivity, or thermostability of enzymes. We have now introduced a crucial element to knowledge-guided targeted mutagenesis in general that helps to solve the numbers problem in directed evolution. We show that the choice of the amino acid (aa) alphabet, as specified by the utilized codon degeneracy, provides the experimenter with a powerful tool in designing "smarter" randomized libraries that require considerably less screening effort. A systematic comparison of two different codon degeneracies was made by examining the relative quality of the identically sized enzyme libraries in relation to the degree of oversampling required in the screening process. The specific example in our case study concerns the conventional NNK codon degeneracy (32 codons/20 aa) versus NDT (12 codons/12 aa). The model reaction is the hydrolytic kinetic resolution of a chiral trans -disubstituted epoxide, catalyzed by the epoxide hydrolase from Aspergillus niger. The NDT library proves to be of much higher quality, as measured by the dramatically higher frequency of positive variants and by the magnitude of catalyst improvement (enhanced rate and enantioselectivity). We provide a statistical analysis that constitutes a useful guide for the optimal design and generation of "smarter" focused libraries. This type of approach accelerates the process of laboratory evolution considerably and can be expected to be broadly applicable when engineering functional proteins in general. [source] Stereoselective Allylation of Ketones: Explanation for the Unusual Inversion of the Induced Stereochemistry in the Auxiliary-Mediated Crotylation and Pentenylation of Butanone by DFT CalculationsCHEMISTRY - A EUROPEAN JOURNAL, Issue 7 2009Abstract The solvent makes the difference: While attack at the Re face of the intermediate oxocarbenium ion becomes less energy demanding with increasing size of R,, it is the solvent effect that makes this attack the main trajectory, leading to inversed stereochemistry (see picture). Auxiliary-mediated domino crotylations and pentenylations of butanone yield homoallylic ethers with two newly formed stereogenic centers. With our norpseudoephedrine-derived auxiliary, we observed the formation of anti isomers exclusively, and the nature of the major isomer was independent of the substrate double bond geometry. Interestingly, there is a switch in induced selectivity when going from crotylation to pentenylation. Here, we present the computational rationalization for this behavior by identification of the relevant transition states (TSs), the energies of which were determined by using the B3LYP/6-31+G(d) level of theory in combination with the PCM/UAKS method to include the effects exerted by the solvent dichloromethane. To quickly narrow down the number of potentially relevant TSs from the whole set of 288 and 864 TSs for the crotylation and pentenylation, respectively, we employed a screening process based on B3LYP//AM1 energies. The predicted selectivities are in good agreement with experimentally determined ones. Furthermore, the obtained results also facilitate an explanation of the selectivities obtained in hexenylations and heptenylations. Finally, activation energies were determined that account for the significantly longer reaction times than those for the domino allylation with unsubstituted trimethylallylsilane. [source] Evaluating transformative practice in the U.S. Postal Service REDRESS programCONFLICT RESOLUTION QUARTERLY, Issue 3 2010Tina Nabatchi Interest in transformative mediation is growing, yet there are few tools with which to assess mediators' use of the transformative model. This study presents a novel way of examining transformative mediation in practice. It triangulates data from training and screening processes and surveys of both mediators and participants to determine whether mediators in the U.S. Postal Service REDRESS program were correctly using transformative mediation. The results indicate that during the period of the study REDRESS mediators were in fact engaged in transformative practice. Such triangulation of data may be a useful approach to assessing transformative practice in other organizations. [source] The Universal Postal Union's strategy for fighting "snail mail" fraud may be the key to making e-commerce saferGLOBAL BUSINESS AND ORGANIZATIONAL EXCELLENCE, Issue 4 2008Virginie Vial Open networks, high-tech or low-tech, are by their nature vulnerable to fraudulent use, and e-commerce platforms are increasingly targets of illegal activity. An international security initiative to reduce drug trafficking through the mails has devised strategies that could also be useful for protecting companies and consumers from online fraud. The author examines the characteristics of networks that make them vulnerable to abuse, and examines the Universal Postal Union's security scheme for working with national postal services to develop a comprehensive database of illegal transactions and upgrade screening processes for detecting them. Finally the author proposes a general framework of action for private companies. © 2008 Wiley Periodicals, Inc. [source] Ultra scale-down of protein refold screening in microwells: Challenges, solutions and applicationBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2009Gareth J. Mannall Abstract Steps for the refolding of proteins from solubilized inclusion bodies or misfolded product often represent bottlenecks in process development, where optimal conditions are typically derived empirically. To expedite refolding optimization, microwell screening may be used to test multiple conditions in parallel. Fast, accurate, and reproducible assays are required for such screening processes, and the results derived must be representative of the process at full scale. This article demonstrates the use of these microscale techniques to evaluate the effects of a number of additives on the refolding of IGF-1 from denatured inclusion bodies, using an established HPLC assay for this protein. Prior to this, microwell refolding was calibrated for scale-up using hen egg-white lysozyme (HEWL) as an initial model protein, allowing us to implement and compare several assays for protein refolding, including turbidity, enzyme activity, and chromatographic methods, and assess their use for microwell-based experimentation. The impact of various microplate types upon protein binding and loss is also assessed. Solution mixing is a key factor in protein refolding, therefore we have characterized the effects of different methods of mixing in microwells in terms of their impact on protein refolding. Our results confirm the applicability and scalability of microwell screening for the development of protein refolding processes, and its potential for application to new inclusion body-derived protein products. Biotechnol. Bioeng. 2009;103: 329,340. © 2008 Wiley Periodicals, Inc. [source] | ||||||||||||||||||||||