In Silico Investigation of Potential Applications of Gamma Carbonic Anhydrases as Catalysts of CO2 Biomineralization Processes: A Visit to the Thermophilic Bacteria Persephonella hydrogeniphila,Persephonella marina,Thermosulfidibacter takaii,and Thermus thermophilus

Carbonic anhydrases (CAs) have been identified as ideal catalysts for CO₂ sequestration. Here, we report the sequence and structural analyses as well as the molecular dynamics (MD) simulations of four γ-CAs from thermophilic bacteria. Three of these, Persephonella marina, Persephonella hydrogeniphila, and Thermosulfidibacter takaii originate from hydrothermal vents and one, Thermus thermophilus HB8, from hot springs. Protein sequences were retrieved and aligned with previously characterized γ-CAs, revealing differences in the catalytic pocket residues. Further analysis of the structures following homology modeling revealed a hydrophobic patch in the catalytic pocket, presumed important for CO₂ binding. Monitoring of proton shuttling residue His69 (P. marina γ-CA numbering) during MD simulations of P. hydrogeniphila and P. marina’s γ-CAs (γ-PhCA and γ-PmCA), showed a different behavior to that observed in the γ-CA of Escherichia coli, which periodically coordinates Zn²⁺. This work also involved the search for hotspot residues that contribute to interface stability. Some of these residues were further identified as key in protein communication via betweenness centrality metric of dynamic residue network analysis. T. takaii’s γ-CA showed marginally lower thermostability compared to the other three γ-CA proteins with an increase in conformations visited at high temperatures being observed. Hydrogen bond analysis revealed important interactions, some unique and others common in all γ-CAs, which contribute to interface formation and thermostability. The seemingly thermostable γ-CA from T. thermophilus strangely showed increased unsynchronized residue motions at 423 K. γ-PhCA and γ-PmCA were, however, preliminarily considered suitable as prospective thermostable CO₂ sequestration agents.     

Teaching robust programming

Robust programming aims to prevent abnormal termination or unexpected actions and requires code to handle bad (invalid or absurd) inputs in a way that is consistent with the developer's intent. For example, if an internal error occurs, the program might terminate gracefully rather than simply failing, providing enough information for the programmer to debug the program and avoiding giving the user additional access or information. This article focuses on teaching these principles.     

Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

Intralesional radiolabeled human monoclonal IgM in human tumor xenografts

Sensory-perceptual abnormalities in people with autism are discussed from two perspectives: published firsthand accounts and existing psychological research evidence. A range of abnormalities, including hyper- and hyposensitivity, sensory distortion and overload, and multichannel receptivity and processing difficulties, are described in firsthand accounts and frequently portrayed as central to the autistic experience. A number of dangers are inherent in uncritically accepting these accounts at face value and in any wider generalization to the autistic population as a whole. Evidence from clinical studies suggests that unusual sensory responses are present in a majority of autistic children, that they are manifested very early in development, and that they may be linked with other aspects of autistic behavior. In addition, experimental studies using a range of indices have found evidence of unusual responses to sensory stimuli in autistic subjects. However the clinical and experimental research to date suffers from serious methodological limitations and more systematic investigation is warranted. Key issues for future psychological research in the area are identified.     

Security issues for downloaded code in mobile phones

'Software defined radio' (SDR) is a technology that will appear in future generations of mobile phones, i.e. following the third-generation mobile phone technology that is currently being defined and developed. Early versions of 'pragmatic' SDR will allow the terminal to be reconfigured at any level of its protocol stack. Ultimately, the 'pure' SDR technology will allow a mobile phone or terminal to have its air interface software configured or reconfigured by other software (or software parameters) that have been downloaded to the terminal, e.g. over the air, or from a remote server via the Internet and one's personal computer (PC). A number of security issues arise with downloaded code that implements the air interface functions, and these may not be obvious simply from looking at the way PC software is updated on-line today. This paper starts with an outline of the code that allows a mobile phone to operate over a particular air interface. This sets the baseline for a discussion of the security issues surrounding the change of this code from one that is fixed and downloaded once only, to code that is reconfigurable during the life of a product.     

A prolog based expert system for the allocation of quality assurance program resources

The worldwide proliferation of fraudulent materials has brought about the need for a new approach to the control of purchased material quality. Nuclear power, defense, aerospace and many other industries are affected by the supply of poor quality clones that presume to be original replacement parts. Safety considerations abound as these highly defective materials are used in systems that are critical to the preservation of human lives. Commonly utilized quality assurance programs have not effectively stopped the influx of fraudulent materials. These programs fail to concentrate inspection efforts on materials and inspection attributes that would effectively prevent the acceptance of fraudulent materials. herein a solution is presented to this problem in the form of an expert system application. Information commonly available in industry is formulated into a knowledge based system wherein advisories are given to the user regarding key purchased material receipt inspection strategies.     

Basic considerations in gastroesophageal reflux disease

The cause of foregut symptoms is often quite uncertain until a comprehensive evaluation has been performed. The critical elements of this evaluation include historic, radiographic, endoscopic, and physiologic data, and most importantly, the insight of a mature diagnostician. Patients who are not evaluated in a comprehensive way are at risk for serious postoperative problems; surgeons who perform interventions without appropriate diagnostic support may have to deal with these unhappy patients. In the long run, a complete workup provides the guidance for treatment and is cost-effective.     

Is electrogastrography a substitute for manometric studies in children with functional gastrointestinal disorders?

We performed simultaneous fasting and fed antroduodenal manometry and EGG in 25 children with functional bowel disorders. Three patients (12%) had an uninterpretable EGG. The manometric studies showed severe neuropathy in six patients; milder neuropathic changes in five patients; postprandial hypomotility in one patient; myopathy in four patients, and normal motility in the remaining six patients. The percentage of tachygastria time (frequency > 3.5 cycles/min) was higher in the patiens with mild (44.1 +/- 15.8%) and severe (48 +/- 19.1%) neuropathy than in the patients with myopathy (20 +/- 16.2%, P < 0.05) or with normal motility (23 +/- 13.3%, P < 0.05). There was a considerable overlap in the percentage of tachygastria and total arrhythmia time among the different study groups. The ratio of post- to preprandial power was significantly higher (2.5 +/- 0.07) in children with normal motility than in the other patients groups. Every child with total arrhythmia time < 35% and a ratio of post- to preprandial power > 2.4 had normal manometry. In summary, EGG differentiated groups of children with normal manometry from others with neuropathic or myopathic changes, but in a minority of patients the study was not interpretable and there was overlap in EGG results between children with normal and abnormal manometry.     

Symptom correlates of attentional improvement following hospitalization for a first episode of affective psychosis

BACKGROUND: This study examined patients with a first-episode of affective psychosis during acute and compensated states in order to determine whether changes in attentional functioning over time were accompanied by changes in the severity of psychotic or affective symptoms. METHODS: Attentional performance was measured in patients (n = 27) using the degraded-stimulus continuous Performance Test (CPT) and symptoms were assessed at the time of index hospitalization, and 2 months after discharge. A comparison group of normal volunteers (n = 31) also performed the CPT two months apart. RESULTS: Patients performed significantly worse than controls at the initial testing but not at follow-up. The improvement in attentional performance significantly correlated with decreased severity of manic symptoms. CONCLUSIONS: Results suggest attentional dysfunction is a state-dependent characteristic of mania, and may provide an additional measure of clinical improvement following treatment.