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.     

Alteration of Sertoli cell differentiation in the presence of carcinoma in situ in human testes

PURPOSE: We investigated Sertoli cells in testicular biopsies with carcinoma in situ (CIS) in respect to cytokeratin expression to elucidate the status of Sertoli cell differentiation adjacent to CIS in human testes. Cytokeratin 18 intermediate filaments indicate a state of undifferentiation usually observed in Sertoli cells of prepubertal testes. MATERIALS AND METHODS: 29 testicular biopsies presenting CIS were investigated by means of immunohistochemistry, using a polyclonal antibody against placental-alkaline phosphatase to detect CIS cells and a monoclonal antibody against human cytokeratin 18 to show expression of cytokeratin 18 intermediate filaments in Sertoli cells. RESULTS: All tubules bearing CIS showed positive cytokeratin expression of Sertoli cells if tubules were devoid of normal germ cells. However, a total of 13 specimen revealed CIS cells together with normal germ cells. In the presence of CIS cells together with round or elongated spermatids, adjacent Sertoli cells did not express cytokeratin immunoreactivity. In the case of combined presence of CIS and spermatogonia and primary spermatocytes, Sertoli cells could be found either immunopositive or immunonegative, and were positive in tubules with CIS and spermatogonia only. CONCLUSIONS: Sertoli cells associated with CIS cells undergo a process of dedifferentiation, seen by the re-expression of cytokeratin intermediate filaments. We suggest that this dedifferentiation results in a loss of Sertoli cell function and leads to a cessation of spermatogenic activity.     

An epidemic of roller-blade injuries in children

Roller blading is a new and increasingly popular leisure activity in many countries. We reviewed 110 consecutive patients with roller-blade injuries between 1 January and 30 June 1996. The patients ranged from 4 to 14 years in age (mean 6.5 years). Eighty-three (75.4%) sustained injuries to the upper limb and 27 (24.5%) injured the lower limb. Fifty-six patients, were girls and 54 were boys. Of the 110 patients, 79 (72.7%) sustained fractures, 28 (25.4%) soft tissue injuries and 3 (2.7%) dislocations. Eighty-three (75.4%) of the patients wore no protective equipment on the limbs. Four months following injury 103 (93.6%) patients were fully recovered. The mean duration of school absence was 3 days. Subsequently 101 children returned to using roller-blades following injury. Seventy-three (66.3%) of these now use protective equipment. We found that injuries were unrelated to age or duration of roller-blading experience or to the brand-name of roller blades used, and that most of our patients wore no protective equipment at the time of injury.     

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.