Fermi Surface of Metallic V_{2}O_{3} from Angle-Resolved Photoemission: Mid-level Filling of e_{g}

Using angle resolved photoemission spectroscopy, we report the first band dispersions and distinct features of the bulk Fermi surface (FS) in the paramagnetic metallic phase of the prototypical metal-insulator transition material V_{2}O_{3}. Along the c axis we observe both an electron pocket and a triangular holelike FS topology, showing that both V 3d a_{1g} and e_{g}^{π} states contribute to the FS. These results challenge the existing correlation-enhanced crystal field splitting theoretical explanation for the transition mechanism and pave the way for the solution of this mystery.

Speed limit of the insulator-metal transition in magnetite.

As the oldest known magnetic material, magnetite (Fe3O4) has fascinated mankind for millennia. As the first oxide in which a relationship between electrical conductivity and fluctuating/localized electronic order was shown, magnetite represents a model system for understanding correlated oxides in general. Nevertheless, the exact mechanism of the insulator-metal, or Verwey, transition has long remained inaccessible. Recently, three-Fe-site lattice distortions called trimerons were identified as the characteristic building blocks of the low-temperature insulating electronically ordered phase. Here we investigate the Verwey transition with pump-probe X-ray diffraction and optical reflectivity techniques, and show how trimerons become mobile across the insulator-metal transition. We find this to be a two-step process. After an initial 300 fs destruction of individual trimerons, phase separation occurs on a 1.5±0.2 ps timescale to yield residual insulating and metallic regions. This work establishes the speed limit for switching in future oxide electronics.

Symmetry of orbital order in Fe3O4 studied by Fe L(2,3) resonant x-ray diffraction.

We studied the symmetry of the Fe 3d wave function in magnetite below the Verwey temperature T(V) with resonant soft-x-ray diffraction. Although the lattice structure of the low-temperature phase of Fe(3)O(4) is well described by the pseudo-orthorhombic Pmca with a slight monoclinic P2/c distortion, we find that the 3d wave function does not reflect the Pmca symmetry, and its distortion toward monoclinic symmetry is by far larger than that of the lattice. The result supports a scenario in which the Verwey transition involves the ordering of t(2g) orbitals with complex-number coefficients.

Inequivalent routes across the Mott transition in V2O3 explored by X-ray absorption.

The changes in the electronic structure of V2O3 across the metal-insulator transition induced by temperature, doping, and pressure are identified using high resolution x-ray absorption spectroscopy at the V pre-K edge. Contrary to what has been taken for granted so far, the metallic phase reached under pressure is shown to differ from the one obtained by changing doping or temperature. Using a novel computational scheme, we relate this effect to the role and occupancy of the a{1g} orbitals. This finding unveils the inequivalence of different routes across the Mott transition in V2O3.

COPD prevalence is increased in lung cancer, independent of age, sex and smoking history.

Chronic obstructive pulmonary disease (COPD) is a common comorbid disease in lung cancer, estimated to affect 40-70% of lung cancer patients, depending on diagnostic criteria. As smoking exposure is found in 85-90% of those diagnosed with either COPD or lung cancer, coexisting disease could merely reflect a shared smoking exposure. Potential confounding by age, sex and pack-yr smoking history, and/or by the possible effects of lung cancer on spirometry, may result in over-diagnosis of COPD prevalence. In the present study, the prevalence of COPD (pre-bronchodilator Global Initiative for Chronic Obstructive Lung Disease 2+ criteria) in patients diagnosed with lung cancer was 50% compared with 8% in a randomly recruited community control group, matched for age, sex and pack-yr smoking exposure (n = 602, odds ratio 11.6; p<0.0001). In a subgroup analysis of those with lung cancer and lung function measured prior to the diagnosis of lung cancer (n = 127), we found a nonsignificant increase in COPD prevalence following diagnosis (56-61%; p = 0.45). After controlling for important variables, the prevalence of COPD in newly diagnosed lung cancer cases was six-fold greater than in matched smokers; this is much greater than previously reported. We conclude that COPD is both a common and important independent risk factor for lung cancer.

Aerial spraying of 2,4,5-T and human birth malformations: an epidemiological investigation.

An investigation of the rate of birth malformations in the Northland region of New Zealand provides no evidence to associate spraying of 2,4,5-trichlorophenoxyacetic acid with the occurrence of any malformation of the central nervous system, including spina bifida. A statistically significant association between spray and malformation is found in the case of talipes. Whether this association indicates a causal relation remains to be established.

Protein, DNA, and virus crystallography with a focused imaging proportional counter.

A set of programs has been developed for rapid collection of x-ray intensity data from protein and virus crystals with a commercially available two-dimensional focused geometry electronic detector. The detector is compact and portable, with unusually high spatial resolution comparable to that used in oscillation photography. It has allowed x-ray data collection on weakly diffracting crystals with large unit cells, as well as more conventional "diffractometer-quality" crystals. The quality of the data is compared with that from oscillation photography and automated diffractometry in the range of unit cells from 96.3 to 383.2 angstroms. Isomorphous and anomalous difference Pattersons, based on detector data, are shown for a variable surface glycoprotein mercury derivative and for a repressor-DNA bromine derivative, which has been solved at 7 angstroms with detector data only.

Probing the non-equilibrium transient state in magnetite by a jitter-free two-color X-ray pump and X-ray probe experiment.

We present a general experimental concept for jitter-free pump and probe experiments at free electron lasers. By generating pump and probe pulse from one and the same X-ray pulse using an optical split-and-delay unit, we obtain a temporal resolution that is limited only by the X-ray pulse lengths. In a two-color X-ray pump and X-ray probe experiment with sub 70 fs temporal resolution, we selectively probe the response of orbital and charge degree of freedom in the prototypical functional oxide magnetite after photoexcitation. We find electronic order to be quenched on a time scale of (30 ± 30) fs and hence most likely faster than what is to be expected for any lattice dynamics. Our experimental result hints to the formation of a short lived transient state with decoupled electronic and lattice degree of freedom in magnetite. The excitation and relaxation mechanism for X-ray pumping is discussed within a simple model leading to the conclusion that within the first 10 fs the original photoexcitation decays into low-energy electronic excitations comparable to what is achieved by optical pump pulse excitation. Our findings show on which time scales dynamical decoupling of degrees of freedom in functional oxides can be expected and how to probe this selectively with soft X-ray pulses. Results can be expected to provide crucial information for theories for ultrafast behavior of materials and help to develop concepts for novel switching devices.

Design effects associated with dietary nutrient intakes from a clustered design of 1 to 14-year-old children.

OBJECTIVE: To calculate intra-cluster and intra-household design effects and intra-class correlation coefficients for dietary nutrients obtained from a 24 h record-assisted recall. DESIGN: Children were recruited using clustered probability sampling. Randomly selected starting-point addresses were obtained with probability proportional to mesh block size. SETTING: Children aged 1-14 years in New Zealand. SUBJECTS: There were 125 children in 50 clusters, giving an average of 2.498 children per cluster. In 15 homes, there were two children for the calculation of intra-household statistics. RESULTS: Intra-cluster design effects ranged from 1.0 for cholesterol, beta-carotene, vitamin A, vitamin D, vitamin E, selenium, fructose and both carbohydrate and protein expressed as their contribution to total energy intakes to 1.552 for saturated fat, with a median design effect of 1.148. Their corresponding intra-cluster correlations ranged from 0 to 0.37, respectively. Intra-household design effects ranged from 1.0 for height to 1.839 for vitamin B(6), corresponding to intra-household correlations of 0 and 0.839. The median intra-household design effect was 1.550. Using a sampling design of two to three households per cluster for estimating dietary nutrient intakes would need, on average, a 15% increase in sample size compared with simple random sampling with a maximum increase of 55% to cover all nutrients. CONCLUSIONS: These data enable sample sizes for dietary nutrients to be estimated for both cluster and non-cluster sampling for children aged 1-14 years. The larger design effects found within households suggest that little extra information may be obtained by sampling more than one child per household.

Purification, crystallization and preliminary X-ray analysis of Mycobacterium tuberculosisfolylpolyglutamate synthase (MtbFPGS).

The gene encoding Mycobacterium tuberculosis FPGS (MtbFPGS; Rv2447c) has been cloned and the protein (51 kDa) expressed in Escherichia coli. The purified protein was crystallized either by the batch method in the presence of adenosine diphosphate (ADP) and CoCl2 or by vapour diffusion in the presence of ADP, dihydrofolate and CaCl2. X-ray diffraction data to approximately 2.0 and 2.6 A resolution were collected at the Stanford Synchrotron Radiation Laboratory (SSRL) for crystals grown under the respective conditions. Both crystals belong to the cubic space group P2(1)3, with a unit-cell parameter of 112.6 and 111.8 A, respectively. Structure determination is proceeding.

The crystal structure of the Leishmania major surface proteinase leishmanolysin (gp63).

BACKGROUND: Despite their medical importance, there is little available structural information for the surface antigens of infectious protozoa. Diseases caused by the protozoan parasite Leishmania are common in many developing countries. Human infection occurs during the bite of infected sandfilies, when Leishmania promastigote cells from the insect gut enter the bloodstream. Promastigotes in the blood parasitize macrophages, often causing serious disease. Leishmanolysin is the predominant protein surface antigen of promastigotes, and is assumed to have a key role during infection. Leishmanolysin is a membrane-bound zinc proteinase, active in situ. Similar molecules exist in other trypanomastid protozoa. RESULTS: Two crystal forms of leishmanolysin were obtained from protein purified from promastigote membranes. A single lead derivative in both crystal forms was used to solve the structure. The structure reveals three domains, two of which have novel folds. The N-terminal domain has a similar structure to the catalytic modules of zinc proteinases. The structure clearly shows that leishmanolysin is a member of the metzincin class of zinc proteinases. CONCLUSIONS: The unexpected metzincin features of the leishmanolysin structure suggest that the metzincin fold may be more widespread than indicated by sequence homologies amongst existing metzincin zinc proteinases. The similarity of the active-site structure to previously well characterized metzincin class zinc proteinases should aid the development of specific inhibitors. These inhibitors might be used to determine the function of leishmanolysin in the insect and during mammalian infection, and may aid the development of drugs for human leishmaniasis.

Purification and crystallization of human cathepsin D.

The two-chain form of human cathepsin D was purified from human spleen with a method utilizing an ion exchange chromatography step prior to the pepstatin affinity column normally used to purify aspartic proteases. The protein was crystallized from 21% polyethylene glycol 8000 at pH 4.0 using the hanging drop vapour diffusion method. Small crystals were used as seeds to grow crystals suitable for X-ray data collection. The crystals diffract to a resolution of 3.2 A and have space group P2(1)2(1)2(1) with unit cell dimensions a = 59.9 A, b = 99.6 A, c = 133.6 A. There are two molecules in the asymmetric unit.

Crystallization and initial crystallographic results for pepstatin A inhibited bovine cathepsin D.

Cathepsin D was purified from bovine liver by a method using two pepstatin A affinity columns. The eluted protein was combined with pepstatin A and the complex crystallized from 15% polyethylene glycol 8000 at pH 5.9. The crystals diffract to a resolution of 3.0 A and have space group P2(1)2(1)2(1) with unit cell dimensions a = 74.8 A, b = 76.0 A, c = 157.7 A. There are two molecules in the asymmetric unit. The structure was solved by molecular replacement using a pepsin search model and both molecules showed clearly interpretable density in the position expected for pepstatin A in a preliminary difference map. The refined model has r.m.s. deviations from ideal bond lengths and angles of 0.014 A and 3.2 degrees, respectively, and a crystallographic R factor of 17%.

Fructosamine concentrations in general population of Kawerau.

We measured fructosamine concentrations in nonfasted serum from 7094 residents (82.8% of the estimated population) of Kawerau, New Zealand, including 65 known diabetic patients (prevalence of 0.92%). Fructosamine results showed a trimodal frequency distribution, with cutting points corresponding to 5th and 95th percentile values. Forty-two diabetic individuals had levels that exceeded the 95th percentile. These individuals had more severe metabolic abnormalities, characterized by lower plasma C-peptide and elevated fasting plasma glucose concentrations. Mean fructosamine values also showed a significant increase with age and a highly significant age-ethnic interaction that paralleled the higher frequency of diabetes in older age groups and among elderly Maori people. However, as a screening method in the general population, fructosamine measurement was diagnostically deficient because of a weak correlation with serum albumin. Arithmetic correction for albumin concentration in the sample did not increase the diagnostic usefulness of the test.

Long-term (5-year) effects of a reduced-fat diet intervention in individuals with glucose intolerance.

OBJECTIVE: To determine whether reducing dietary fat would reduce body weight and improve long-term glycemia in people with glucose intolerance. RESEARCH DESIGN AND METHODS: A 5-year Follow-up of a 1-year randomized controlled trial of a reduced-fat ad libitum diet versus a usual diet. Participants with glucose intolerance (2-h blood glucose 7.0-11.0 mmol/l) were recruited from a Workforce Diabetes Survey. The group that was randomized to a reduced-fat diet participated in monthly small-group education sessions on reduced-fat eating for 1 year. Body weight and glucose tolerance were measured in 136 participants at baseline 6 months, and 1 year (end of intervention), with follow-up at 2 years (n = l04), 3 years (n = 99), and 5 years (n = 103). RESULTS: Compared with the control group, weight decreased in the reduced-fat-diet group (P < 0.0001); the greatest difference was noted at 1 year (-3.3 kg), diminished at subsequent follow-up (-3.2 kg at 2 years and -1.6 kg at 3 years), and was no longer present by 5 years (1.1 kg). Glucose tolerance also improved in patients on the reduced-fat diet; a lower proportion had type 2 diabetes or impaired glucose tolerance at 1 year (47 vs. 67%, P < 0.05), but in subsequent years, there were no differences between groups. However, the more compliant 50% of the intervention group maintained lower fasting and 2-h glucose at 5 years (P = 0.041 and P = 0.026 respectively) compared with control subjects. CONCLUSIONS: The natural history for people at high risk of developing type 2 diabetes is weight gain and deterioration in glucose tolerance. This process may be ameliorated through adherence to a reduced fat intake

Microalbuminuria in a middle-aged workforce. Effect of hyperglycemia and ethnicity.

OBJECTIVE: To determine the prevalence of microalbuminuria in a mixed, ethnic population and to find the extent that ethnic variation in microalbuminuria can be explained by abnormal glucose metabolism, obesity, hypertension, hypertriglyceridemia, and life-style factors. RESEARCH DESIGN AND METHODS: Urinary albumin concentrations were measured in 5467 middle-aged Maori, Pacific Islander, and European workers who participated in a health-screening survey of 46 New Zealand companies. Participants provided a first-voided, morning urine sample; had a 75-g oral glucose tolerance test; had weight, height, and blood pressure measured; and completed a self-administered questionnaire about past medical history and sociodemographic status. RESULTS: A significantly higher prevalence of microalbuminuria was found in individuals with new cases of diabetes mellitus (24.1%), in cases of diabetes mellitus previously diagnosed (20.6%), and in those with impaired glucose tolerance (16.1%) compared with nondiabetic individuals (4.0%). Moreover, in the general population, a piecewise linear relationship was detected between albuminuria and plasma glucose with significant changes of slope corresponding with 2 h plasma glucose concentrations (95% confidence interval) of 6.7 (6.4-7.0) and 9.2 (8.6-9.8) mM, respectively. After adjusting for sex, obesity, hypertension, hypertriglyceridemia, cigarette smoking, and heavy alcohol consumption in a multivariate model, glycemia was the most significant determinant of urinary albumin concentrations in all three ethnic groups. However, blood glucose concentrations did not completely explain the higher relative risk (95% confidence interval) of microalbuminuria in Maori (5.97; 4.48-7.78) and Pacific Islander (5.33; 4.13-6.87) workers compared with European workers. CONCLUSIONS: Of the variables investigated, hyperglycemia was the most important factor explaining the high prevalence of microalbuminuria in Maori and Pacific Islander workers compared with the European workers. However, only 14.9% of the variation in urinary albumin concentrations was found in our multivariate model, and we have speculated on the contribution of other factors such as diet and coexisting renal diseases.

Multiple functions of pro-parts of aspartic proteinase zymogens.

The importance of aspartic proteinases in human pathophysiology continues to initiate extensive research. With burgeoning information on their biological functions and structures, the traditional view of the role of activation peptides of aspartic proteinases solely as inhibitors of the active site is changing. These peptide segments, or pro-parts, are deemed important for correct folding, targeting, and control of the activation of aspartic proteinase zymogens. Consequently, the primary structures of pro-parts reflect these functions. We discuss guidelines for formation of hypotheses derived from comparing the physiological function of aspartic proteinases and sequences of their pro-parts.

Low serum albumin. Association with diabetes mellitus and other cardiovascular risk factors but not with prevalent cardiovascular disease or carotid artery intima-media thickness. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.

We examined the association of serum albumin concentration with diabetes mellitus and other cardiovascular risk factors, prevalent cardiovascular disease, and ultrasonographically assessed carotid artery intima-media thickness using data from 45- to 64-year-old adults in the Atherosclerosis Risk in Communities (ARIC) Study. The mean albumin concentration was 0.04 to 0.12 g/L lower in participants with diabetes and 0.02 to 0.06 g/L lower in those with cardiovascular disease, compared to participants without these conditions. However, lower serum albumin level was also correlated with most traditional risk factors and hemostatic variables. On adjustment for these, there was essentially no association between serum albumin and prevalent cardiovascular disease. Likewise, there was no association between albumin and carotid intima-media thickness (a marker of atherosclerosis). While hypoalbuminemia may be a marker for chronic disease and perhaps renal loss of albumin, it seems unlikely that it is an important cause of atherosclerosis.

Mandibulofacial dysostosis in Hutterite sibs: a possible recessive trait.

We report on two sisters with mandibulofacial dysostosis (MFD). Both parents were examined carefully by clinical, radiographic, audiologic, and cephalometric methods. Neither showed evidence of the MFD gene. Photographs of three grandparents and examination of one disclosed no evidence of MFD. The parents are from the Hutterite Brethren and are consanguineous. Examination of the literature on MFD disclosed a number of other families with affected sibs and apparently normal parents. These families raise the possibility of an autosomal recessive form of MFD or some other explanation such as germinal mosaicism, chromosome rearrangement, or delayed mutation. For our family, the recurrence risk is probably 25%, but since germinal mosaicism cannot be excluded, it could be as high as 50%.

The Bowen-Conradi syndrome -- a highly lethal autosomal recessive syndrome of microcephaly, micrognathia, low birth weight, and joint deformities.

This paper describes six Hutterite children from five families who appear to have been affected by the same syndrome that was described in two brothers by Bowen and Conradi [1]. Our additional cases confirm that the major features of the syndrome include porportionate intrauterine growth retardation, microcephaly, micrognathia, a prominent nose, rocker-bottom feet, joint limitation, and failure to thrive, with death within the first year of life. Bowen-Conradi syndrome is an autosomal recessive trait and pedigree records show that all six families now known are related to each other through two couples born in the late 1700s but that there are additional earlier possible sources of the responsible gene. The differential diagnosis of this syndrome is discussed.