A Density Functional Theory Study on the Active Center of Fe-Only Hydrogenase: Characterization and Electronic Structure of the Redox States

<p>We have carried out extensive density functional theory (DFT) calculations for possible redox states of the active center in Fe-only hydrogenases. The active center is modeled by [(H(CH(3))S)(CO)(CN(-))Fe(p)(mu-DTN)(mu-CO)Fe(d)(CO)(CN(-))(L)](z) (z is the net charge in the complex; Fe(p)= the proximal Fe, Fe(d) = the distal Fe, DTN = (-SCH(2)NHCH(2)S-), L is the ligand that bonds with the Fed at the trans position to the bridging CO). Structures of possible redox states are optimized, and CO stretching frequencies are calculated. By a detailed comparison of all the calculated structures and the vibrational frequencies with the available experimental data, we find that (i) the fully oxidized, inactive state is an Fe(II)-Fe(II) state with a hydroxyl (OH(-)) group bonded at the Fe(d), (ii) the oxidized, active state is an Fe(II)-Fe(l) complex which is consistent with the assignment of Cao and Hall (J. Am. Chem. Soc. 2001, 123, 3734), and (iii) the fully reduced state is a mixture with the major component being a protonated Fe(l)-Fe(l) complex and the other component being its self-arranged form, Fe(II)-Fe(II) hydride, Our calculations also show that the exogenous CO can strongly bond with the Fe(II)-Fe(l) species, but cannot bond with the Fe(l)-Fe(l) complex. This result is consistent with experiments that CO tends to inhibit the oxidized, active state, but not the fully reduced state. The electronic structures of all the redox states have been analyzed. It is found that a frontier orbital which is a mixing state between the e(g) of Fe and the 2pi of the bridging CO plays a key role concerning the reactivity of Fe-only hydrogenases: (1) it is unoccupied in the fully oxidized, inactive state, half-occupied in the oxidized, active state, and fully occupied in the fully reduced state; (ii) the e(g)-2pi orbital is a bonding state, and this is the key reason for stability of the low oxidation states, such as Fe(l)-Fe(l) complexes; and (iii) in the e(g)-2pi orbital more charge accumulates between the bridging CO and the Fe(d) than between the bridging CO and the Fe(p), and the occupation increase in this orbital will enhance the bonding between the bridging CO and the Fe(d), leading to the bridging-CO shift toward the Fe(d).</p>

Is screening for Factor V Leiden and Prothrombin G20210A Mutations in Renal Transplantation worthwhile? Results of a large single-center U.K. study

This single center study is the largest series of renal transplant recipients and donors screened for the commonest prothrombotic genotypes. A total of 562 transplant recipients and 457 kidney donors were genotyped for the factor V Leiden and prothrombin G20210A mutations. The prevalence of heterozygous factor V Leiden was 3.4% and 2.6% and prothrombin G20210A was 2.0% and 1.1% in recipients and donors, respectively, similar frequencies to that of the general U.K. population. The 30-day and 1-year graft survival rates in recipients with thrombophilic mutations were 93% and 93%, compared with 88% and 82% in patients without these mutations (log-rank P =0.34). Thrombophilia in recipients (odds ratio 0.55; confidence interval 0.06-2.29; P =0.56) or in donors (odds ratio 1.53; confidence interval 0.27-5.74; P =0.46) did not correlate with graft loss at 30 days after transplantation. In contrast to recent reports, this study did not demonstrate an association between thrombophilia and renal allograft loss, and routine screening is not recommended.

Reduced vision in older adults with age related macular degeneration interferes with ability to care for self and impairs role as carer

Aim: To study the relation between visual impairment and ability to care for oneself or a dependant in older people with age related macular degeneration (AMD). Method: Cross sectional study of older people with visual impairment due to AMD in a specialised retinal service clinic. 199 subjects who underwent visual function assessment (fully corrected distance and near acuity and contrast sensitivity in both eyes), followed by completion of a package of questionnaires dealing with general health status (SF36), visual functioning (Daily Living Tasks Dependent on Vision, DLTV) and ability to care for self or provide care to others. The outcome measure was self reported ability to care for self and others. Three levels of self reported ability to care were identified—inability to care for self (level 1), ability to care for self but not others (level 2), and ability to care for self and others (level 3). Results: People who reported good general health status and visual functioning (that is, had high scores on SF36 and DLTV) were more likely to state that they were able to care for self and others. Similarly people with good vision in the better seeing eye were more likely to report ability to care for self and others. People with a distance visual acuity (DVA) worse than 0.4 logMAR (Snellen 6/15) had less than 50% probability of assigning themselves to care level 3 and those with DVA worse than 1.0 logMAR (Snellen 6/60) had a probability of greater than 50% or for assigning themselves to care level 1. Regression analyses with level of care as the dependent variable and demographic factors, DLTV subscales, and SF36 dimensions as the explanatory variables confirmed that the DLTV subscale 1 was the most important variable in the transition from care level 3 to care level 2. The regression analyses also confirmed that the DLTV subscale 2 was the most important in the transition from care level 3 to care level 1. Conclusions: Ability to care for self and dependants has a strong relation with self reported visual functioning and quality of life and is adversely influenced by visual impairment. The acuity at which the balance of probability shifts in the direction of diminished ability to care for self or others is lower than the level set by social care agencies for provision of support. These findings have implications for those involved with visual rehabilitation and for studies of the cost effectiveness of interventions in AMD.

A machine vision approach to the grading of crushed aggregate

The grading of crushed aggregate is carried out usually by sieving. We describe a new image-based approach to the automatic grading of such materials. The operational problem addressed is where the camera is located directly over a conveyor belt. Our approach characterizes the information content of each image, taking into account relative variation in the pixel data, and resolution scale. In feature space, we find very good class separation using a multidimensional linear classifier. The innovation in this work includes (i) introducing an effective image-based approach into this application area, and (ii) our supervised classification using wavelet entropy-based features.

An automated machine vision system for the histological grading of cervical intraepithelial neoplasia (CIN)

<p>The histological grading of cervical intraepithelial neoplasia (CIN) remains subjective, resulting in inter- and intra-observer variation and poor reproducibility in the grading of cervical lesions. This study has attempted to develop an objective grading system using automated machine vision. The architectural features of cervical squamous epithelium are quantitatively analysed using a combination of computerized digital image processing and Delaunay triangulation analysis; 230 images digitally captured from cases previously classified by a gynaecological pathologist included normal cervical squamous epithelium (n = 30), koilocytosis (n = 46), CIN 1 (n = 52), CIN 2 (n = 56), and CIN 3 (n=46). Intra- and inter-observer variation had kappa values of 0.502 and 0.415, respectively. A machine vision system was developed in KS400 macro programming language to segment and mark the centres of all nuclei within the epithelium. By object-oriented analysis of image components, the positional information of nuclei was used to construct a Delaunay triangulation mesh. Each mesh was analysed to compute triangle dimensions including the mean triangle area, the mean triangle edge length, and the number of triangles per unit area, giving an individual quantitative profile of measurements for each case. Discriminant analysis of the geometric data revealed the significant discriminatory variables from which a classification score was derived. The scoring system distinguished between normal and CIN 3 in 98.7% of cases and between koilocytosis and CIN 1 in 76.5% of cases, but only 62.3% of the CIN cases were classified into the correct group, with the CIN 2 group showing the highest rate of misclassification. Graphical plots of triangulation data demonstrated the continuum of morphological change from normal squamous epithelium to the highest grade of CIN, with overlapping of the groups originally defined by the pathologists. This study shows that automated location of nuclei in cervical biopsies using computerized image analysis is possible. Analysis of positional information enables quantitative evaluation of architectural features in CIN using Delaunay triangulation meshes, which is effective in the objective classification of CIN. This demonstrates the future potential of automated machine vision systems in diagnostic histopathology. Copyright (C) 2000 John Wiley and Sons, Ltd.</p>

Prevalence of early and late age-related macular degeneration in a rural population in Northern India: The INDEYE Feasibility Study

PURPOSE. To assess the prevalence of age-related macular degeneration (AMD) in a rural population in Northern India. METHODS. In a pilot feasibility study, 1443 people (median age, 60 years; 52% women), were identified from enumeration of the 50+ age group in 11 randomly sampled villages from a rural, periurban district of Haryana, Northern India. Of those identified, 87% attended an eye examination that included digital fundus photography. Fundus images were graded at a single reading center using definitions from the Wisconsin Age-Related Maculopathy Grading System. RESULTS. Fundus photographs were available for 1101 participants. Overall, 28.8% of participants had ungradable fundus images due to cataract. Including all with ungradable images in the denominator, the prevalence of soft drusen was 34.0% (95% confidence interval [CI] 26.1–42.9); of soft indistinct drusen, 2.2% (95% CI, 1.1–4.4); and of pigmentary irregularities, 10.8% (95% CI, 7.1–16.1). There were 15 (1.4%) cases of late-stage AMD (95% CI, 0.8–2.3) with the prevalence rising from 0.4% in the 50- to 59-year age range to 4.6% in those aged 70 years or older. CONCLUSIONS. Drusen and pigmentary irregularities are common among the rural northern Indian population. The prevalence of late AMD is similar to that encountered in Western settings and is likely to contribute significantly to the burden of vision loss in older people in the developing world.