Origins of electronic band gap reduction in Cr/N codoped TiO2.

Recent studies indicated that noncompensated cation-anion codoping of wide-band-gap oxide semiconductors such as anatase TiO2 significantly reduces the optical band gap and thus strongly enhances the absorption of visible light [W. Zhu et al., Phys. Rev. Lett. 103, 226401 (2009)]. We used soft x-ray spectroscopy to fully determine the location and nature of the impurity levels responsible for the extraordinarily large (∼1 eV) band gap reduction of noncompensated codoped rutile TiO2. It is shown that Cr/N codoping strongly enhances the substitutional N content, compared to single element doping. The band gap reduction is due to the formation of Cr 3d3 levels in the lower half of the gap while the conduction band minimum is comprised of localized Cr 3d and delocalized N 2p states. Band gap reduction and carrier delocalization are critical elements for efficient light-to-current conversion in oxide semiconductors. These findings thus raise the prospect of using codoped oxide semiconductors with specifically engineered electronic properties in a variety of photovoltaic and photocatalytic applications.

In vivo wireless ethanol vapor detection in the Wistar rat.

Traditional alcohol studies measure blood alcohol concentration to elucidate the biomedical factors that contribute to alcohol abuse and alcoholism. These measurements require large and expensive equipment, are labor intensive, and are disruptive to the subject. To alleviate these problems, we have developed an implantable, wireless biosensor that is capable of measuring alcohol levels for up to six weeks. Ethanol levels were measured in vivo in the interstitial fluid of a Wistar rat after administering 1 g/kg and 2 g/kg ethanol by intraperitoneal (IP) injection. The data were transmitted wirelessly using a biosensor selective for alcohol detection. A low-power piezoresistive microcantilever sensor array was used with a polymer coating suitable for measuring ethanol concentrations at 100% humidity over several hours. A hydrophobic, vapor permeable nanopore membrane was used to screen liquid and ions while allowing vapor to pass to the sensor from the subcutaneous interstitial fluid.

A Drosophila homolog of bovine smg p25a GDP dissociation inhibitor undergoes a shift in isoelectric point in the developmental mutant quartet.

The Drosophila developmental mutation quartet causes late larval lethality and small imaginal discs and, when expressed in the adult female, has a lethal effect on early embryogenesis. These developmental defects are associated with mitotic defects, which include a low mitotic index in larval brains and incomplete separation of chromosomes in mitosis in the early embryo. quartet mutations also have a biochemical effect, i.e., a basic shift in isoelectric point in three proteins. We have purified one of these proteins, raised an antibody to it, and isolated and sequenced its cDNA. At the amino acid level, the sequence shows 68% identity and 81% similarity to bovine smg p25a GDP dissociation inhibitor (GDI), a regulator of ras-like small GTPases of the rab/SEC4/YPT1 subfamily. The correlation between a basic shift in isoelectric point in Drosophila GDI in quartet mutant tissue and the quartet developmental phenotype raises the possibility that a posttranslational modification of GDI is necessary for its function and that GDI function is essential for development.

A deletion of the 3' end of the Drosophila melanogaster hsp70 gene increases stability of mutant mRNA during recovery from heat shock.

hsp40, an X-ray-induced deletion mutant of the major Drosophila melanogaster heat shock protein gene hsp70, was shown to be incorrectly regulated at the translational level. hsp40 protein synthesis persisted at a high level after the release from heat shock, whereas hsp70 protein production was rapidly repressed. This result was observed both in flies heterozygous for the hsp40 gene and in tissue culture cells transfected with the truncated gene. Analysis of the transcription of the hsp40 gene indicated that its mRNA, unlike hsp70 mRNA, was not actively destabilized after a return to control temperatures, permitting prolonged production of the mutant protein.

Alemtuzumab induces caspase-independent cell death in human chronic lymphocytic leukemia cells through a lipid raft-dependent mechanism.

Alemtuzumab is a humanized IgG1 kappa antibody directed against CD52, a glycosyl-phosphatidylinositol linked cell-membrane protein of unknown function. Herein, we demonstrate that alemtuzumab promotes rapid death of chronic lymphocytic leukemia (CLL) cells in vitro, in a complement and accessory cell free system. Using minimal detergent solubilization of CLL membranes, we found that CD52 colocalizes with ganglioside GM-1, a marker of membrane rafts. Fluorescence microscopy revealed that upon crosslinking CD52 with alemtuzumab+anti-Fc IgG, large patches, and in many cases caps, enriched in CD52 and GM-1 formed upon the CLL cell plasma membrane. Depletion of membrane cholesterol or inhibition of actin polymerization significantly diminished the formation of alemtuzumab-induced caps and reduced alemtuzumab-mediated CLL cell death. We compared alemtuzumab-induced direct cytotoxicity, effector cell-mediated toxicity and complement-mediated cytotoxicity of CLL cells to normal T cells. The direct cytotoxicity and observed capping was significantly greater for CLL cells as compared to normal T cells. Cell-mediated and complement-mediated cytotoxicity did not significantly differ between the two cell types. In summary, our data support the hypothesis that alemtuzumab can initiate CLL cell death by crosslinking CD52-enriched lipid rafts. Furthermore, the differential direct cytotoxic effect suggests that CD52 directed antibodies could possibly be engineered to more specifically target CLL cells.

Immunologic, biochemical, and ultrastructural characterization of the leukemia cell in F344 rats.

Immunologic, biochemical, and morphologic characteristics of the mononuclear cell from the leukemia of F344 rats were determined. The cells were morphologically similar to large granular lymphocytes (LGL). Surface marker analysis revealed Fc gamma receptors, no Fc gamma receptor or complement receptor activity, and an inability to spontaneously rosette guinea pig erythrocytes. Leukemia cells also had a surface immunoglobulin that hemagglutinated normal rat erythrocytes. The surface immunoglobulin and Fc gamma receptors dissociated from the cell after 2 hours of in vitro incubation, but Fc gamma receptor activity was reexpressed after 6 hours of in vitro incubation. Cells were capable of adherence to glass surfaces but had a low capacity for phagocytosis of latex beads. Cytochemical analysis revealed a consistent, strongly positive reaction for esterase that was sensitive to NaF. The cytochemical profile of the leukemia cell was similar to that described for LGL.

Parenteral nutrition in marrow transplant recipients after discharge from the hospital.

The use of parenteral nutrition (PN) following discharge from the hospital and its relation to patient characteristics were evaluated retrospectively in 246 marrow transplant recipients. PN was used in 65% of all patients. Patients with leukemia, regardless of age, sex, type of leukemia, remission status, irradiation schedule, laminar air flow isolation and donor sex match, required more frequent and more prolonged PN than patients with aplastic anemia. Children required PN most often for failure to thrive and adults for stomatitis. There was no significant difference in frequency or duration of PN among 24 patients with acute myelogenous leukemia randomized to receive cyclosporine or methotrexate therapy and among 28 patients with acute lymphoblastic leukemia randomized to interferon or no interferon. We conclude that outpatient PN presents a valuable addition to posttransplant supportive care. It shortens the duration of hospitalization both by earlier discharge of patients still requiring PN and by avoiding readmission to the hospital for the purpose of PN.

Nutritional support in marrow graft recipients with single versus double lumen right atrial catheters.

To determine the comparative efficiency of single and double lumen right atrial catheters, marrow transplant recipients were evaluated during a 26-month period retrospectively. Calories and protein infused as a percent of the amount ordered was calculated by week from initiation of total parenteral nutrition through day 28 posttransplantation. Data from 1979 reflected initial technical difficulties, showing no significant difference between groups. Patients with double lumen catheters received significantly greater (P less than 0.05) calories during the first 3 weeks after transplant in 1980 and 1981. A similar trend was seen in protein infusion. A significantly greater proportion of patients with double lumen catheters received at least 90% of the ordered total parenteral nutrition during the first 3 weeks after transplant in both years. These results suggest that the ability to infuse total parenteral nutrition in ordered amounts can be accomplished using the double lumen catheter.

Oxidative phosphorylation and aspects of calcium metabolism in myocardia of hypercholesterolaemic swine with moderate coronary atherosclerosis.

Aspects of myocardial oxidative phosphorylation and Ca2+ metabolism were studied in a swine model in which coronary atherosclerosis was induced by a combination of denudation of the endothelium of the coronary arteries plus 7--11 months of feeding a high fat--high cholesterol diet. By microscopy, a moderate amount of coronary atherosclerosis was present at the time of sacrifice, and 2 of the 14 swine hearts had old myocardial infarcts. Myocardial mitochondria from grossly normal areas showed partial uncoupling and decreased state 3 O2 uptake with 3 of 4 substrates tested. In addition, Ca2+ stimulated mitochondrial respiration was decreased in the atherosclerotic swine. In the sarcoplasmic reticulum Ca2+ uptake under conditions of heavy loading was greater in the atherosclerotic swine than in control animals. The degree of atherosclerosis was not great enough to suggest that persistent myocardial ischaemia was present. Possibly coronary artery spasm induced an intermittent ischaemia resulting in the metabolic abnormalities observed, or the changes may have been brought about by the effects of the high fat--high cholesterol diet on subcellular membranes.

Do estrogens improve bone mineral density in osteoporotic women over age 65?

A retrospective analysis of our experience with estrogen and fluoride treatment in 91 patients with postmenopausal osteopenia followed for 6-47 months has been performed. Treatment included calcium (1000 mg/day) and either conjugated estrogens (0.625 mg/day) or sodium fluoride (50 mg/day), or both. All patients had at least two serial dual-photon spinal bone mineral density measurements performed 6 months or more apart. Estrogen treatment was associated with increased bone mineral density (5.3%/year), as was fluoride alone (7.5%/year). Estrogen and fluoride together were additive (9.6%/year). In women over age 65 the estrogen effect was just as great (6.9%/year) as in younger women. Estrogen benefit occurred predominantly in the first 18 months of treatment (7.0%/year), after which time changes in bone mineral density were similar to those in untreated controls, who showed stable bone mineral density. We conclude that aggressive estrogen and fluoride treatment tailored to the severity of the individual's postmenopausal osteopenia results in short-term improvement in spinal bone mineral density. These data further support that elderly women respond to estrogen replacement therapy with absolute and relative increments in bone density similar to those in younger women.

Cytopathic feline leukemia viruses cause apoptosis in hemolymphatic cells.

Certain isolates of the oncoretrovirus feline leukemia virus (FeLV) are strongly cytopathic for hemolymphatic cells. A major cytopathicity determinant is encoded by the SU envelope glucoprotein gp70. Isolates with subgroup C SU gp70 genes specifically induce apoptosis in hemolymphatic cells but not fibroblasts. In vitro exposure of feline T-cells to FeLV-C leads first to productive viral replication, next to virus-induced cell agglutination, and lastly to apogenesis. This in vitro phenomenon may explain the severe progressive thymic atrophy and erythroid aplasia which follow viremic FeLV-C infection in vivo. Inappropriate apoptosis induction has also been hypothesized to explain the severe thymico-lymphoid atrophy and progressive immune deterioration associated with isolates of FeLV containing variant envelope genes. The influence of envelope hypervariability (variable regions 1 [Vr1] and 5 [Vr5] on virus tropism, viremia induction, neutralizing antibody development and cytopathicity is discussed. Certain potentially cytopathic elements in FeLV SU gp70 Vr5 may derive from replication-defective, poorly expressed, endogenous FeLVs. Other more highly conserved regions in FeLV TM envelope p15E may also influence apoptosis induction.

Interaction of Sec4 with GDI proteins from bovine brain, Drosophila melanogaster and Saccharomyces cerevisiae. Conservation of GDI membrane dissociation activity.

Rab GDP dissociation inhibitor (Rab GDI), will induce the dissociation of GDP-bound rab3A from synaptic membranes and will inhibit GDP dissociation from Sec4, a member of the Rab subgroup of the Ras GTPase superfamily which is required for exocytosis in Saccharomyces cerevisiae. We report that Rab GDI releases GDP-bound Sec4 from yeast membranes. dGDI, a Drosophila homologue can similarly inhibit GDP dissociation from Sec4 and release GDP-bound Sec4 from yeast membranes. An activity partially purified from yeast cytosol dissociates GDP-bound Sec4 from yeast membranes, suggesting that yeast also possess a GDI protein that functions to recycle Sec4 from its target membrane.

Computerized tomography assessment of women with weight changes associated with adjuvant treatment for breast cancer.

It is common for women undergoing treatment for breast cancer to gain weight, although the characteristics of the weight change have not been described. We investigated the changes in abdominal fat accumulation that accompanied the change in weight associated with treatment for breast cancer in longitudinal and cross-sectional clinical studies in 34 women aged 39-73 y with early-stage primary breast cancer. Computerized tomography scans of abdominal subcutaneous and visceral adipose depots, bioelectrical impedance measurements of body fat mass, and measurements of body weight and girth were obtained early in the course of treatment and 6 mo later (longitudinal study; n = 8) or within 12 mo of treatment (cross-sectional study; n = 26). The longitudinal study found that, irrespective of the direction of weight change, seven of eight women gained body fat and lost lean body mass. In the five women who gained weight (median: 3.2 kg) two lost and three gained subcutaneous adipose fat (median: 19%) whereas all gained visceral fat (median: 23%). In the cross-sectional study 19 women gained weight and 7 lost weight or had stable weight since diagnosis. Change in weight was correlated with abdominal subcutaneous adipose fat (r = 0.39; P = 0.06) and hip circumference (r = 0.43; P = 0.03) but not abdominal visceral fat, the ratio of subcutaneous to visceral fat, or the ratio of waist to hip size. In the longitudinal sample, weight gain resulted in a variable response in subcutaneous adipose volumes but a consistent increase in visceral adipose depot. Although these results are preliminary, it appeared that regardless of weight gain or loss women were likely to lose lean body mass and gain fat mass during treatment for breast cancer.

Effect of medical records' checklists on implementation of periodic health measures.

Recent re-evaluation of preventive health care has resulted in more limited and directed guidelines; nonetheless, physician compliance has remained poor. This study assessed whether an inexpensive reminder system of preventive care checklists would improve physician implementation of periodic health measures. Residents in internal medicine were randomly placed into two groups: one received a copy of the appropriate checklist with each patient's medical record; the other did not. After one year, 200 randomly selected records were audited to determine the proportion of recommendations implemented for each patient. Residents who received checklists performed appropriate preventive health measures at a significantly higher rate than those who did not (0.56 +/- 0.26 versus 0.39 +/- 0.22, p less than 0.002). The actual use of the checklist to record the results was associated with an even higher rate of compliance compared with instances in which the checklists were provided but not used and instances in which checklists were not received (0.70 +/- 0.21 versus 0.44 +/- 0.24 and 0.39 +/- 0.22, respectively, p less than 0.002). These data suggest that a physician's use of simple checklists can provide an inexpensive and effective means of improving implementation of periodic health maintenance.

Temporal relationships and IL-2 dependency of prolactin-induced lymphocyte proliferation.

Recombinant preparations of human prolactin (hPRL) and interleukin 2 (hIL-2) as well as monoclonal antibodies to these growth factors were used to study the synergistic interaction of PRL and IL-2 in Nb2 rat lymphoma lactogen-dependent cells. It was shown that IL-2 stimulated Nb2 cell proliferation in lactogen-free culture medium. Experiments with short-term exposure to growth factor demonstrated that PRL was required only during the initial 12 h of incubation while IL-2 was mitogenic regardless of the time it was added. Antibody to IL-2 partially inhibited both PRL- and IL-2-induced proliferation whereas antibody to PRL significantly decreased PRL but not IL-2-induced proliferation. These findings suggest that the complete mitogenic effect of PRL on Nb2 cells requires stimulation of IL-2 production.

Infectious feline leukaemia virus is erythrosuppressive in vitro.

The direct effect of the feline leukaemia virus (FeLV) on erythroid colony formation in vitro was investigated. Bone marrow mononuclear cells (BMMC) from FeLV-naïve, specific-pathogen-free (SPF), adult cats were inoculated with FeLVs of characterized strains and biologically cloned subgroups and the subsequent development of colony forming units-erythroid (CFUE) and burst forming units-erythroid (BFUE) and colony forming units-granulocyte-macrophage (CFUGM) was monitored. Exposure to the anaemia-causing Kawakami-Theilen strain of FeLV (FeLV-KT), a phenotypic mixture of subgroups A, B, and C, caused constant depression of day 2 CFUE (to 47% of sham-inoculated controls), day 4 CFUE (41% of controls), and day 10 BFUE (38% of controls). CFUGM were unaffected. The lymphoma-causing Rickard strain of FeLV (FeLV-R-TL) caused sporadic depression of CFUE and BFUE. In contrast, neither FeLV-R passaged through feline embryonic kidney fibroblasts (FeLV-R-CRFK) nor biologically cloned, subgroup-specific, FeLVs of fibroblast origin, caused decrements in CFUE or BFUE, suggesting that fibroblast passage attenuated the direct erythrosuppressive effect of FeLV. Suppression of CFUE and BFUE by lymphoma cell-origin FeLV was dependent on infectious virus and was associated with FeLV replication by the cultured myelomonocytic precursor cells. Attenuation of infectivity by heat or u.v. restored CFUE and BFUE development. Examination of the relationship between viral infectivity (VI), viral protein concentration, and CFUE suppression showed that the infectious FeLV was 20-fold more effective than u.v.-inactivated FeLV as an inhibitor of erythrogenesis in vitro.

Vibrational lifetime of bond-center hydrogen in crystalline silicon

The lifetime of the stretch mode of bond-center hydrogen in crystalline silicon is measured to be T1 = 7.8+/-0.2 ps with time-resolved, transient bleaching spectroscopy. The low-temperature spectral width of the absorption line due to the stretch mode converges towards its natural width for decreasing hydrogen concentration C(H), and nearly coincides with the natural width for C(H) approximately 1 ppm. The lifetimes of the Si-H stretch modes of selected hydrogen-related defects are estimated from their spectral widths and shown to range from 1.6 to more than 37 ps.

Oral protein intake and the risk of acute graft-versus-host disease after allogeneic marrow transplantation.

The possibility that antigenically active protein macromolecules affect the risk of developing acute graft-versus-host disease (aGVHD) was investigated in a cohort of patients who underwent allogeneic marrow transplantation for hematologic malignancy (n = 575). Daily records of food intake from transplant through discharge or death were evaluated for grams of total protein and summed over consecutive 4-day intervals. The day of onset of aGVHD was partitioned into 4-day time intervals such that assessments of food intake preceded onset of aGVHD by 3-6 days. Acute GVHD developed in 308 (54%) patients. The cumulative incidence of aGVHD among patients eating any amount of protein was lower (4-13%) than that of patients not eating protein (8-19%) for each of the time intervals through day 21 post-transplant; the relative risk associated with protein intake, adjusted for patient and transplant characteristics that are correlated with the occurrence of aGVHD, ranged from 0.23 (95% confidence interval (CI) 0.09, 0.63) to 0.83 (CI 0.46, 1.51). A proportional hazards regression analysis, using protein intake as a time-dependent covariate, confirmed these results. The findings of this study provide no support for the hypothesis that intake of protein-containing foods during the first 3 weeks after marrow transplantation increases the risk of aGVHD.

Demonstration of heterogeneity in gestational diabetes by a 400-kcal breakfast meal tolerance test.

To evaluate the metabolic basis of gestational glucose intolerance (gestational diabetes), the response of normal pregnant women (N=6) and lean (N=23), and obese (N=12) gestational diabetics to the physiologic challenge of a 400-kcal mixed meal breakfast tolerance test was studied. Obese patients with gestational diabetes were more hyperglycemic than the lean gestational diabetics in both the fasting and postprandial periods. Women with gestational diabetes had a more prolonged glycemic response and a later insulin response to meal stimulation than normal control subjects. Fasting and postprandial insulin levels were higher in the obese gestational diabetes group, whereas those of lean subjects fell below the values of the control group. The percent specific binding of insulin to red blood cell receptors was lower in both gestational diabetes groups than in control subjects, with the most marked decrease in the obese group. Mean fasting plasma levels of total cholesterol and triglyceride and plasma glucagon levels during the meal tolerance test were not significantly different among the three groups. Obese gestational diabetics had significantly larger infants and placentas than lean gestational diabetics. These findings, taken together, suggest that the pathophysiology of gestational diabetes differs between obese and lean patients. Lean gestational diabetics appear to develop glucose intolerance on the basis of relative insulin deficiency in contrast to obese gestational diabetics who manifest glucose intolerance characterized by insulin resistance, hyperinsulinemia, and decreased insulin binding to red blood cell receptors.

Hepatitis C.

In the latter half of the 20th century, HCV emerged as the most common cause of chronic liver disease, and will likely remain so. Since its initial discovery in 1989, rapid progress has been made in our understanding of the virology, epidemiology, natural history, diagnosis, and treatment of HCV. Over the next few decades, as further advancements are made, superior treatment options will become available.