Complete RNA inverse folding: computational design of functional hammerhead ribozymes

Nanotechnology and synthetic biology currently constitute one of the most innovative, interdisciplinary fields of research, poised to radically transform society in the 21st century. This paper concerns the synthetic design of ribonucleic acid molecules, using our recent algorithm, RNAiFold, which can determine all RNA sequences whose minimum free energy secondary structure is a user-specified target structure. Using RNAiFold, we design ten cis-cleaving hammerhead ribozymes, all of which are shown to be functional by a cleavage assay. We additionally use RNAiFold to design a functional cis-cleaving hammerhead as a modular unit of a synthetic larger RNA. Analysis of kinetics on this small set of hammerheads suggests that cleavage rate of computationally designed ribozymes may be correlated with positional entropy, ensemble defect, structural flexibility/rigidity and related measures. Artificial ribozymes have been designed in the past either manually or by SELEX (Systematic Evolution of Ligands by Exponential Enrichment); however, this appears to be the first purely computational design and experimental validation of novel functional ribozymes. RNAiFold is available at http://bioinformatics.bc.edu/clotelab/RNAiFold/.Comment: 17 pages, 2 tables, 7 figures, final version to appear in Nucleic Acids Researc

The Sun also Sets: Ending the Life of a Software Product

Abstract. Sunsetting a software product is a painful and frustrating process, whether it happens in times of crisis or in an organized and planned manner. It is surprising that little information is available on how to perform sunsetting and it appears to be a blind spot in software product management literature. This paper describes the sunsetting method and provides practitioners with a welldefined process of how software products must be taken out of development, maintenance, and finally use. With the sunsetting method, product managers will have as little trouble as possible based on the experiences of others. The process description is elaborated using a method description. Furthermore, three retrospective case studies have been conducted to evaluate the method

Detecting Dairy Cow Behavior Using Vision Technology

The aim of this study was to investigate using existing image recognition techniques to predict the behavior of dairy cows. A total of 46 individual dairy cows were monitored continuously under 24 h video surveillance prior to calving. The video was annotated for the behaviors of standing, lying, walking, shuffling, eating, drinking and contractions for each cow from 10 h prior to calving. A total of 19,191 behavior records were obtained and a non-local neural network was trained and validated on video clips of each behavior. This study showed that the non-local network used correctly classified the seven behaviors 80% or more of the time in the validated dataset. In particular, the detection of birth contractions was correctly predicted 83% of the time, which in itself can be an early warning calving alert, as all cows start contractions several hours prior to giving birth. This approach to behavior recognition using video cameras can assist livestock management

‘Mind the Gap’ between ecosystem services classification and strategic decision making

Ecosystem services (ES) are increasingly embedded in policy agendas, but if and how policy actors are considering them is not often reported. This study assesses the extent to which ES were considered by key policy actors involved in the strategic decision-making process leading to an innovative large-scale Dutch coastal management project. We analysed retrospective interviews to ascertain which ES were considered and how they were described by policy actors. Over half of the quotes (118/228) and 16 out of the 17 interviewees referred to three broad ES categories, with high degrees of adoption: coastal safety, recreation and cognitive development (learning by doing). The broad terms ‘nature’ and ‘spatial quality’ were also referenced often (36 times). Our findings suggest that broad, unspecified ecosystem services were adopted highly by the policy actors, while specific ecosystem service categories were rarely considered. Relatable and comprehensible cultural ecosystem services also constituted critical arguments for policy actors in their strategic decision making. We reflect that ambiguous, broad terms can help to garner support and unite efforts across disciplinary and institutional boundaries. For ES to align with relevant aspects of decision making, a ‘translation step’ between ES research and decision making might be required and ambiguity should be acknowledged.</p

Anesthesia for massive retrosternal goiter with severe intrathoracic tracheal narrowing: the challenges imposed -A case report-

Anesthetic management of patients with mediastinal masses remains challenging as acute cardiorespiratory decompensation may follow induction of anesthesia. We describe a 57 year old lady with massive retrosternal goiter and severe intrathoracic tracheal compression who had a total thyroidectomy. Comprehensive contingency plans were an essential prerequisite for successful management of difficult airway, including multidisciplinary involvement of otorhinolaryngologic and cardiothoracic surgeons preparing for rigid bronchoscopy and cardiopulmonary bypass. Awake oral fiberoptic intubation was performed under dexmedetomidine sedation. Severe tracheal narrowing necessitated usage of a 5.0 mm uncuffed flexometallic endotracheal tube. Anesthesia was maintained with sevoflurane and dexmedetomidine infusion with target controlled infusion of remifentanil as analgesia. No muscle relaxant was given. Surgical manipulation led to intermittent total tracheal compression and inadequate ventilation. The tumor was successfully removed via the cervical approach. A close working relationship between anesthesiologists and surgeons was the key to the safe use of anesthesia and uneventful recovery of this patient

Toward an understanding of transfusion-related acute lung injury: statement of a consensus panel

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73845/1/j.0041-1132.2004.04347.x.pd

Suboptimal clinical response to ciprofloxacin in patients with enteric fever due to Salmonella spp. with reduced fluoroquinolone susceptibility: a case series

BACKGROUND: Salmonella spp. with reduced susceptibility to fluoroquinolones have higher than usual MICs to these agents but are still considered "susceptible" by NCCLS criteria. Delayed treatment response to fluoroquinolones has been noted, especially in cases of enteric fever due to such strains. We reviewed the ciprofloxacin susceptibility and clinical outcome of our recent enteric fever cases. METHODS: Salmonella enterica Serotype Typhi (S. Typhi) and Serotype Paratyphi (S. Paratyphi) blood culture isolates (1998–2002) were tested against nalidixic acid by disk diffusion (DD) and agar dilution (AD) and to ciprofloxacin by AD using NCCLS methods and interpretive criteria. Reduced fluoroquinolone susceptibility was defined as a ciprofloxacin MIC of 0.125–1.0 mg/L. The clinical records of patients treated with ciprofloxacin for isolates with reduced fluoroquinolone susceptibility were reviewed. RESULTS: Seven of 21 (33%) S. Typhi and S. Paratyphi isolates had reduced susceptibility to fluoroquinolones (MIC range 0.125–0.5 mg/L). All 7 were nalidixic acid resistant by DD (no zone) and by AD (MIC 128- >512 mg/L). The other 14 isolates were nalidixic acid susceptible and fully susceptible to ciprofloxacin (MIC range 0.015–0.03 mg/L). Five of the 7 cases were treated initially with oral ciprofloxacin. One patient remained febrile on IV ciprofloxacin until cefotaxime was added, with fever recurrence when cefotaxime was discontinued. Two continued on oral or IV ciprofloxacin alone but had prolonged fevers of 9–10 days duration, one was switched to IV beta-lactam therapy after remaining febrile for 3 days on oral/IV ciprofloxacin and one was treated successfully with oral ciprofloxacin. Four of the 5 required hospitalization. CONCLUSIONS: Our cases provide further evidence that reduced fluoroquinolone susceptibility of S. Typhi and S. Paratyphi is clinically significant. Laboratories should test extra-intestinal Salmonella spp. for reduced fluoroquinolone susceptibility

The effectiveness of local air pollution control in Lancashire

This thesis examines the implementation of air pollution control at the local level within the UK. Focusing upon the local air pollution control regime (LAPC) that is regulated by local authorities under the provisions of Part One of the Environmental Protection Act 1990, the research assesses whether this system has been effective in controlling localised emissions from industrial processes. To place the research in context, it essentially evaluates the implementation of LAPC with reference to its main objectives: to reduce industrial emissions and improve local air quality, to provide greater clarity and certainty for business and to allow the public greater access to local environmental information. The methodology adopted to undertake the research was based upon grounded theory and naturalistic inquiry. As such, the research programme was structured in phases where initially, essential baseline data was collected on the LAPC system. This quantitative data provided the foundations from which more detailed qualitative work was undertaken in the field in subsequent phases of the research. This allowed the research to build towards theory utilising an emergent, yet structured research design. As the research progressed, a range of complementary methods were used to collect data about the LAPC system. Initially, the research critically evaluated the major Reports that had been written on LAPC in order to establish benchmarks from which implementation of the LAPC system could be assessed. To keep the research within defined limits, a case study approach was adopted, using Lancashire as the case study area. Under the first phase of the research a questionnaire was used to survey the process operators within the region in order to collect baseline information about their processes and to obtain their views and perceptions of the LAPC system. Under the second phase qualitative research was carried out in the field. This involved detailed, semi-structured, faceto-face interviews with the process operators and the DETR and examination of documentary evidence within the Public Registers held by Lancashire's local authorities. The phased approach allowed the research to explore progressively deeper into the key areas associated with the implementation of the LAPC system. In particular, the research examined local authority enforcement and administration of the LAPC system to assess their regulatory performance and to determine the strategies they adopt to achieve compliance. The research also focused upon the process operators to assess their capacity to comply with the duties and responsibilities placed upon them under LAPC. The work offers a new perspective as it focuses upon both regulators and operators alike and examines their performance from the outset of LAPC to its closing stages. The research findings allow conclusions to be drawn on the relationship that exists between these "stakeholders" and the regulatory conditions that exist within the system. The research findings suggest that local authorities and process operators have had difficulty in discharging their duties under the LAPC system. For various reasons, the capacity of the regulators and the operators to achieve compliance has been compromised. The difficulties that the stakeholders have faced in striving to come to terms with the LAPC system have influenced their compliance strategies and affected the relationship that exists between them. This research identifies and examines these difficulties and assesses their performance under such conditions