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Alkylation of -amino acid derived iminoesters with Baylis-Hillman (BH) reaction template based allyl bromides/allyl acetates followed by acidic hydrolysis furnished -methylene--substituted-pyroglutamates and -alkylidene pyroglutamates respectively. Application of these methodologies has been demonstrated in the synthesis of fused [3.2.0]--lactam--lactones. Further, substrate controlled stereoselective alkylation of L-threonine derived oxazoles with BH reaction based allyl bromides and acetates yielded optically pure -methylene--substituted pyroglutamates, and -alkylidene pyroglutamates. These methodologies have been applied in the preparation of chiral [3.2.0] heterobicyclic pyroglutamates containing hydroxyethyl side chain. All the synthesized pyroglutamates have been evaluated for their anti-cancer and enzyme proteasome inhibition activity.

Objectives. The social determinants of health (SDH) include factors apart from genes and biology that affect population health. Zoning is an urban planning tool that influences neighborhood built environments. We describe the methods and results of a health impact assessment (HIA) of a rezoning effort in Baltimore, Maryland, called TransForm Baltimore. We highlight findings specific to physical activity, violent crime, and obesity.Methods. We conducted a multistage HIA of TransForm Baltimore using HIA practice guidelines. Key informant interviews identified focus areas for the quantitative assessment. A literature review and a zoning code analysis evaluated potential impacts on neighborhood factors including physical activity, violent crime, and obesity. We estimated potential impacts in high- and low-poverty neighborhoods. The findings resulted in recommendations to improve the health-promoting potential of TransForm Baltimore.Results. Mixed-use and transit-oriented development were key goals of TransForm Baltimore. Health impacts identified by stakeholders included walkability and healthy communities. For Baltimore residents, we estimated that (1) the percentage of people living in districts allowing mixed-use and off-premise alcohol outlets would nearly triple, (2) 18% would live in transit-oriented development zones, and (3) all residents would live in districts with new lighting and landscaping guidelines. Limiting the concentration of off-premise alcohol outlets represented an opportunity to address health promotion.Conclusions. Changes to Baltimore's zoning code could improve population health including decreasing violent crime. HIAs are an important platform for applying SDH to public health practice. This HIA specifically linked municipal zoning policy with promoting healthier neighborhoods.

Radiographic osteopenia is regularly observed after implant removal from a fracture or femoral osteotomy but has not been objectively quantified. Hardware removal is generally performed months to years after the index event (fracture or osteotomy) when full activity has been resumed. Objectively demonstrable bone mineral deficiency affects fracture risk. Hardware removal may facilitate the return to normal bone mineral density. Children who had dual-energy X-ray absorptiometry scans following femoral implant removal were retrospectively reviewed to assess the percent of change in bone mineral density and change in Z-scores. The femoral neck and the lateral distal femora were scanned, comparing the operated side with unaffected femur as a control. Sixteen children were included. Patients demonstrated up to 15.4% (average, 4.8%) less bone mineral density in the femoral neck region, up to 43% less (average, 16.5%) in the metabolically active distal metaphyseal region, and up to 18.1% less (average, 6.3%) in the transitional region. No statistical difference was noted in the diaphy-seal region. A statistically significant decrease in Z-score was noted when plate and screw constructs (average change, −0.97 SD) as compared with intramedullary nail constructs (average change, −0.33 SD) were used. Children can exhibit statistically significant decreases in bone mineral density in the femoral neck and distal femur following femoral implant removal, with plate and screw constructs demonstrating a greater effect than intramedullary (load sharing) devices. This has implications for return to activity and suggests that implant removal may be important in restoration of bone strength in children.

We report a refinement in implicit water of the previously published solution structure of the Grb7-SH2 domain bound to the erbB2 receptor peptide pY1139. Structure quality measures indicate substantial improvement, with residues in the most favored regions of the Ramachandran plot increasing by 14 and with WHAT IF statistics (Vriend, G. J. Mol. Graph., 1990, 8(1), 52-56) falling closer to expected values for well-refined structures.

The molecular orientation and electronic structure of hexa-peri-hexabenzocoronene (HBC) deposited on Ag(111) was investigated in the mono- and multilayer regime by near edge X-ray absorption fine structure spectroscopy (NEXAFS), scanning tunneling and scanning force microscopy (STM and SFM), and ultraviolet photoelectron spectroscopy (UPS). We found that the molecular orientation changed as a function of coverage, exhibiting a transition from flat lying HBC in the monolayer to molecules being 43° inclined relative to the substrate plane in the multilayer. This structural transition was accompanied by a rigid shift of molecular energy levels by 0.3 eV toward higher binding energy between mono- and multilayer. In addition, broadening of the highest molecular levels by ca. 0.35 eV was observed in the multilayer, suggesting the formation of extended intermolecular energy bands.

A highly concerted strategy for the synthesis of symmetrical type-VI β-turn mimics was formulated. A proof of concept is presented in the synthesis of a spirobicyclic peptidomimetic of Pro-Pro-Pro-NH2, compound 6. The formation of an unusual adduct that was encountered in the process also is reported. This approach is potentially general for type-VI β-turn mimics where the i + 1 and i + 2 residues are identical.

A practically simple three-component chiral derivatizing protocol for determining the enantiopurity of 13 chiral primary amines by 1H NMR spectroscopic analysis is described, including analysis of those that contain remote stereocenters.

Viral capsids are dynamic structures which self-assemble and undergo a series of structural transformations to form infectious viruses. The dsDNA bacteriophage P22 is used as a model system to study the assembly and maturation of icosahedral dsDNA viruses. The P22 procapsid, which is the viral capsid precursor, is assembled from coat protein with the aid of scaffolding protein. Upon DNA packaging, the capsid lattice expands and becomes a stable virion. Chemical cross-linking analyzed by mass spectrometry was used to identify residue specific inter- and intra-subunit interactions in the P22 procapsids. All the intersubunit cross-links occurred between residues clustered in a loop region (residues 157−207) which was previously identified by mass spectrometry based on hydrogen/deuterium exchange and biochemical experiments. DSP and BS3 which have similar distance constraints (12 Å and 11.4 Å, respectively) cross-linked the same residues between two subunits in the procapsids (K183−K183), whereas DST, a shorter cross-linker, cross-linked lysine 175 in one subunit to lysine 183 in another subunit. The replacement of threonine with a cysteine at residue 182 immediately adjacent to the K183 cross-linking site resulted in slow spontaneous disulfide bond formation in the procapsids without perturbing capsid integrity, thus suggesting flexibility within the loop region and close proximity between neighboring loop regions. To build a detailed structure model, we have predicted the secondary structure elements of the P22 coat protein, and attempted to thread the prediction onto identified helical elements of cryoEM 3D reconstruction. In this model, the loop regions where chemical cross-linkings occurred correspond to the extra density (ED) regions which protrude upward from the outside of the capsids and face one another around the symmetry axes. Keywords: bacteriophage P22 • capsid interactions • chemical cross-linking • mass spectrometry

Pro-Leu-Gly-NH2 (PLG), in addition to its endocrine effects, possesses the ability to modulate dopamine D2 receptors within the central nervous system. However, the precise binding site of PLG is unknown. Potential photoaffinity-labeling ligands of the PLG binding site were designed as tools to be used in the identification of the macromolecule that possesses this binding site. Six different photoaffinity-labeling ligands were designed and synthesized on the basis of the γ-lactam PLG peptidomimetic 1. The 4-azidobenzoyl and 4-azido-2-hydroxybenzoyl photoaffinity-labeling moieties were placed at opposite ends of PLG peptidomimetic 1 to generate a series of ligands that potentially could be used to map the PLG binding site. All of the compounds that were synthesized possessed activity comparable to or better than PLG in enhancing [3H]-N-propylnorapomorphine agonist binding to dopamine receptors. Photoaffinity ligands that were cross-linked to the receptor preparation produced a modulatory effect that was either comparable to or greater than the increase in agonist binding produced by the respective ligands that were not cross-linked to the dopamine receptor. The results indicate that these photoaffinity-labeling agents are binding at the same allosteric site as PLG and PLG peptidomimetic 1.

We have recently identified a series of compounds that efficiently inhibit anthrax lethal factor (LF) metallo-protease. Here we present further structure−activity relationship and CoMFA (comparative molecular field analysis) studies on newly derived inhibitors. The obtained 3D QSAR model was subsequently compared with the X-ray structure of the complex between LF and a representative compound. Our studies form the basis for the rational design of additional compounds with improved activity and selectivity.

ErbB signaling through extracellular signal-regulated kinase (ERK) has been implicated in regulating the expression of ErbB ligands in hyperproliferative skin disorders and wound healing. Here, we characterize the process of autocrine ERK activation in cultured normal human keratinocytes (NHKs) subjected to growth factor (GF) deprivation. Basal ERK phosphorylation was lower after 48 h than after 24 h of GF deprivation, and lowest at 30-60 min after an additional medium change. ERK phosphorylation was markedly increased by low concentrations of epidermal growth factor (EGF) (0.2-1 ng/ml) that provoked only a limited increase in ErbB1 tyrosine phosphorylation and internalization. Basal ErbB tyrosine phosphorylation and ERK phosphorylation were inhibited by two different ErbB receptor tyrosine kinase inhibitors, by the ErbB1-specific neutralizing monoclonal antibody 225 IgG, by two different metalloproteinase inhibitors, and by neutralizing antibodies against amphiregulin (AR). In contrast, these responses were unaffected by neutralizing antibodies against other ErbB1 ligands or the ErbB2 inhibitors geldanamycin and AG825. The time course of autocrine ERK phosphorylation correlated with the appearance of soluble AR, and two different metalloproteinase inhibitors blocked AR release. These results define an amphiregulin- and ErbB1-dependent mechanism by which autocrine ERK activation is maintained in NHKs, even when ErbB1 autophosphorylation and internalization are limited.

Previous studies demonstrated that tolerance to the long-term neurotoxic effects of methamphetamine on dopamine neurons could be induced by pretreating with multiple injections of escalating doses of methamphetamine. The mechanism(s) underlying this tolerance phenomenon is unknown. Some recent studies suggested that aberrant vesicular monoamine transporter-2 (VMAT-2) and dopamine transporter function contribute to neurotoxic effects of methamphetamine. Hence, the purpose of this study was to explore the role of the VMAT-2 and dopamine transporter in the induction of tolerance to the longterm persistent dopaminergic deficits caused by methamphetamine. A second purpose was to investigate the potential role of hyperthermia and alterations in brain methamphetamine distribution in this tolerance. Results revealed that the methamphetamine pretreatment regimen attenuated both the acute methamphetamine-induced decrease in VMAT-2 function 2 h after the methamphetamine challenge administration and its resulting persistent dopamine deficits without attenuating the acute methamphetamine-induced decreases in dopamine transporter uptake. Furthermore, pretreatment with methamphetamine prior to a high-dose methamphetamine challenge administration also attenuated the acute methamphetamine-induced redistribution of VMAT-2 immunoreactivity within the nerve terminal. This protection was not due to alterations in concentration of methamphetamine in the brain because both the methamphetamine- and saline-pretreated rats had similar amounts of methamphetamine and amphetamine at 30 min to 2 h after the last methamphetamine challenge injection. In summary, these data are the first to demonstrate an association between the prevention of acute alterations in vesicular dopamine uptake and the development of tolerance to the neurotoxic effects of methamphetamine.

In budding yeast, activation of the small Ras-like GTPase Tem1 triggers exit from mitosis and cytokinesis. Tem1 is regulated by Bub2/Bfa1, a two-component GTPase-activating protein (GAP), and by Lte1, a putative guanine nucleotide exchange factor. Lte1 is confined to the bud cortex, and its spatial separation from Tem1 at the spindle pole body (SPB) is important to prevent untimely exit from mitosis. The pathways contributing to Lte1 asymmetry have not been elucidated. Here we show that establishment of Lte1 at the cortex occurs by an actin-independent mechanism, which requires activation of Cdc28/Cln kinase at START and Cdc42, a key regulator of cell polarity and cytoskeletal organisation. This defines a novel role for Cdc42 in late mitotic events. In turn, dissociation of Lte1 from the cortex in telophase depends on activation of the Cdc14 phosphatase. Ectopic expression of Cdc14 at metaphase results in premature dephosphorylation of Lte1 coincident with its release from the cortex. In vitro phosphatase assays confirm that Lte1 is a direct substrate for Cdc14. Our results suggest that the asymmetry in Lte1 localisation is imposed by Cdc28-dependent phosphorylation. Finally, we report a mutational analysis undertaken to investigate intrinsic Lte1 determinants for localisation. Our data suggest that an intrameric interaction between the N-and C-terminal regions of Lte1 is important for cortex association.

One possible reason why regeneration remains enigmatic is that the dominant organisms used for studying regeneration are not amenable to genetic approaches. We mutagenized zebrafish and screened for temperature-sensitive defects in adult fin regeneration. The nightcap mutant showed a defect in fin regeneration that was first apparent at the onset of regenerative outgrowth. Positional cloning revealed that nightcap encodes the zebrafish orthologue of mps1, a kinase required for the mitotic checkpoint. mps1 expression was specifically induced in the proximal regeneration blastema, a group of cells that normally proliferate intensely during outgrowth. The nightcap mutation caused severe defects in these cells. However, msxb-expressing blastemal cells immediately distal to this proliferative region did not induce mps1 and were retained in mutants. These results indicate that the proximal blastema comprises an essential subpopulation of the fin regenerate defined by the induction and function of Mps1. Furthermore, we show that molecular mechanisms of complex tissue regeneration can now be dissected using zebrafish genetics.

Cephalosporin antibiotics with structures that include the heterocyclic leaving group 1-methyltetrazole-5-thiol (MTT) can cause hypoprothrombinemia and hemorrhage as a result of MTT-dependent inhibition of the gamma-carboxylation of glutamate. The structure of cefazolin also includes a heterocyclic thiol, 2-methyl-1,3,4-thiadiazole-5-thiol (MTD), and this compound can also inhibit the gamma-carboxylation of glutamate. However, unlike MTT, which is known to be present in vivo after the administration of drugs that include this structure, there have been no reports that MTD is present in vivo after cefazolin administration. We set out to determine whether MTD might be present in the tissues of patients treated with cefazolin prior to surgery. To do that, we took advantage of the fact that heterocyclic thiols can undergo S-methylation catalyzed by the genetically polymorphic drug-metabolizing enzyme thiopurine S-methyltransferase (TPMT). Initially, we tested recombinant human TPMT as a "reagent" to S-methylate MTD. MTD was a substrate for TPMT-catalyzed S-methylation, with an apparent K(m) value of 63 micro M. Recombinant TPMT, with [(14)C-methyl]S-adenosyl-L-methionine as a cosubstrate, was then used to radioactively label a methyl acceptor substrate present in liver and kidney cytosol preparations from patients who had been treated preoperatively with cefazolin. Pooled renal cytosol from 10 of those patients was used to purify and isolate the methylated product by reverse-phase high-performance liquid chromatography. That methylated compound coeluted with S-methyl MTD. When the methylated product was subjected to tandem mass spectrometry, it was identified as S-methyl MTD. Therefore, MTD is present in the tissues of patients treated with cefazolin. These observations also raise the possibility that the TPMT genetic polymorphism may represent a risk factor for cefazolin-induced hypoprothrombinemia since subjects who genetically lack TPMT would be unable to catalyze this MTD biotransformation pathway.

In eukaryotes an abnormal spindle activates a conserved checkpoint consisting of the MAD and BUB genes that results in mitotic arrest at metaphase. Recently, we and others identified a novel Bub2-dependent branch to this checkpoint that blocks mitotic exit. This cell-cycle arrest depends upon inhibition of the G-protein Tem1 that appears to be regulated by Bfa1/Bub2, a two-component GTPase-activating protein, and the exchange factor Lte1. Here, we find that Bub2 and Bfa1 physically associate across the entire cell cycle and bind to Tem1 during mitosis and early G1. Bfa1 is multiply phosphorylated in a cell-cycle-dependent manner with the major phosphorylation occurring in mitosis. This Bfa1 phosphorylation is Bub2-dependent. Cdc5, but not Cdc15 or Dbf2, partly controls the phosphorylation of Bfa1 and also Lte1. Following spindle checkpoint activation, the cell cycle phosphorylation of Bfa1 and Lte1 is protracted and some species are accentuated. Thus, the Bub2-dependent pathway is active every cell cycle and the effect of spindle damage is simply to protract its normal function. Indeed, function of the Bub2 pathway is also prolonged during metaphase arrests imposed by means other than checkpoint activation. In metaphase cells Bub2 is crucial to restrain downstream events such as actin ring formation, emphasising the importance of the Bub2 pathway in the regulation of cytokinesis. Our data is consistent with Bub2/Bfa1 being a rate-limiting negative regulator of downstream events during metaphase.

Nuclear morphological changes during apoptosis are very distinct and effector caspases have been implicated to play a central role in these processes. To investigate this in greater detail we examined the effect of blocking caspase activity and its activation on the nuclear morphological change in Jurkat T cells undergoing apoptosis after staurosporine treatment. In the presence of caspase inhibitors, like benzyloxycarbonyl-Val-Ala-Asp fluoro-methylketone (z-VAD-FMK), N-acetyl Tyr-Val-Ala-Asp chloromethylketone (Ac-YVAD-CMK) and benzyloxy-carbonyl-Asp-Glu-Val-Asp (OMe) fluoromethylketone (z-DEVD-FMK), staurosporine-treated Jurkat cells displayed a nuclear morphological change distinct from that of normal and apoptotic cells. This nuclear morphological change is an early event, characterised by convoluted nuclei with cavitations, and clumps of chromatin abutting to inner regions of the nuclear envelope between the nuclear pores. Both the nuclear envelope and endoplasmic reticulum were grossly dilated. This pre-apoptotic nuclear change precedes the externalisation of phosphatidylserine, chromatin condensation and DNA laddering, and can be dissociated from the formation of high molecular weight DNA fragments and cell shrinkage. Although cytochrome c efflux from the mitochondria and the processing of caspase-3 were observed in Jurkat cells with pre-apoptotic nuclear morphology, caspase-2, -6, -7 and -8 were not activated. In the presence of z-DEVD-FMK or Ac-YVAD-CMK, caspase-3 was processed to both the p17 and p20 fragments in staurosporine-treated cells, but only to p20 fragment in the presence of z-VAD-FMK. However, the caspase-3 substrate, poly(ADP ribose) polymerase was not cleaved in the presence of z-VAD-FMK, despite >70% of the cells have pre-apoptotic nuclei. In addition, caspase-3 null MCF-7 cells also undergo pre-apoptotic nuclear change when treated with staurosporine in the presence of caspase inhibitors, indicating that caspase-3 is not required for the early nuclear morphological change in cells undergoing apoptosis. Although cell death in staurosporine-treated Jurkat cells was markedly delayed, they eventually die without discernible downstream apoptotic features. Other apoptotic stimuli like etoposide and the heavy metal chelator, N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine also induced this nuclear morphological change in Jurkat cells in the presence of z-VAD-FMK. In summary, the effector caspases are not involved in early nuclear morphological change, which precedes the conventional hallmark morphological changes associated with chemical-induced apoptosis.

The Skn7 response regulator has previously been shown to play a role in the induction of stress-responsive genes in yeast, e.g., in the induction of the thioredoxin gene in response to hydrogen peroxide. The yeast Heat Shock Factor, Hsf1, is central to the induction of another set of stress-inducible genes, namely the heat shock genes. These two regulatory trans-activators, Hsf1 and Skn7, share certain structural homologies, particularly in their DNA-binding domains and the presence of adjacent regions of coiled-coil structure, which are known to mediate protein-protein interactions. Here, we provide evidence that Hsf1 and Skn7 interact in vitro and in vivo and we show that Skn7 can bind to the same regulatory sequences as Hsf1, namely heat shock elements. Furthermore, we demonstrate that a strain deleted for the SKN7 gene and containing a temperature-sensitive mutation in Hsf1 is hypersensitive to oxidative stress. Our data suggest that Skn7 and Hsf1 cooperate to achieve maximal induction of heat shock genes in response specifically to oxidative stress. We further show that, like Hsf1, Skn7 can interact with itself and is localized to the nucleus under normal growth conditions as well as during oxidative stress.

We previously isolated the SKN7 gene in a screen designed to isolate new components of the G1-S cell cycle transcription machinery in budding yeast. We have now found that Skn7 associates with Mbp1, the DNA-binding component of the G1-S transcription factor DSC1/MBF. SKN7 and MBP1 show several genetic interactions. Skn7 overexpression is lethal and is suppressed by a mutation in MBP1. Similarly, high overexpression of Mbp1 is lethal and can be suppressed by skn7 mutations. SKN7 is also required for MBP1 function in a mutant compromised for G1-specific transcription. Gel-retardation assays indicate that Skn7 is not an integral part of MBF. However, a physical interaction between Skn7 and Mbp1 was detected using two-hybrid assays and GST pulldowns. Thus, Skn7 and Mbp1 seem to form a transcription factor independent of MBF. Genetic data suggest that this new transcription factor could be involved in the bud-emergence process.

The homoleptic amides [M(NMe2)5] (M 4;= 4;Nb 1 or Ta 2; the latter is characterised by a structural study) reacted with the carborane nido-C2B9H13 to eliminate two equivalents of HNMe2 and generate the dicarbollide half-sandwich tris(dimethylamide) complexes [M(C2B9H11)(NMe2)3] (M 4;= 4;Nb 3 or Ta 4). The crystal structures of isomorphous 3 and 4 have been determined and reveal two NMe2 ligands in a vertical orientation and the third one in a horizontal orientation with respect to the η5-co-ordinated face of the C2B9H11 ligand. The electronic factors responsible for the amide ligand orientations in these complexes are explored using qualitative MO arguments. Complexes 3 and 4 reacted with CO2 and CS2 to yield the tris(carbamate) [M(C2B9H11)(O2CNMe2)3] (M 4;= 4;Nb 5 or Ta 7) and tris(dithiocarbamate) [M(C2B9H11)(S2CNMe2)3] (M 4;= 4;Nb 6 or Ta 8) complexes, respectively. The crystal structures of 6 and 7 show two (dithio)carbamate ligands in horizontal and one in vertical orientation, demonstrating the similarity between the σ,π-donor frontier orbitals of the ligands NMe2 and X2CNMe2 in 4 and 6 or 7 respectively.

Results of an investigation into the sensitivity to two types of inspection error of link sampling procedures described by Harischchandra and Srivenkataramana are reported. Relevant compound distributions are derived. Some comparisons with results obtained in a similar investigation for standard double sampling are also given.

We have shown previously that the Swi5 transcription factor regulates the expression of the SIC1 Cdk inhibitor in late mitosis. This suggests that Swi5 might control other genes with roles in ending mitosis. We identified a gene with a Swi5-binding site in the promoter that encoded a protein with high homology to Pcl2, a cyclin-like protein that associates with the Cdk Pho85. This gene, PCL9, is indeed regulated by Swi5 in late M phase, the only cyclin known to be expressed at this point in the cell cycle. The Pcl9 protein is associated with a Pho85-dependent protein kinase activity, and the protein is unstable with peak levels occurring in late M phase. PCL2 is already known to be expressed in late G1 and we find that, in addition, it is also regulated by Swi5 in telophase. The expression of PCL2 and PCL9 at this stage of the cell cycle implies a role for the Pho85 Cdk at the end of mitosis. Consistent with this a synthetic interaction was observed between pho85delta and strains deleted for SIC1, SWI5, and SPO12. These and other studies support the notion that the M/G1 switch is a major cell cycle transition.

Sources of error in A-aDO2 calculated from blood stored in plastic and glass syringes. J. Appl. Physiol. 82(1): 196-202, 1997.—We studied the effects of time delay on blood gases, pH, and base excess in blood stored in glass and plastic syringes on ice and the effects of resulting errors on calculated alveolar-to-arterial PO2 difference (A-aDO2). Matched samples of dog whole blood were tonometered with gas mixtures of 5% CO2-12% O2-83% N2 (mixture A), 10% CO2-5% O2-85% N2 (mixture B), and 2.88% CO2-4% O2-93.12% N2 (mixture C). Tonometered blood samples were transferred to 5-ml glass (5G), 5-ml plastic (5P), and 3-ml plastic (3P) syringes and stored on ice. Blood gases were measured every 1 h up to 6 h. In 5G, PO2 progressively decreased in blood tonometered with mixture A but rose in blood tonometered with mixtures B and C. O2 saturation progressively fell in all cases. In 5G, blood PCO2 progressively rose regardless of which gas mixture was used, and pH as well as base excess progressively fell. The rise in PO2 was faster in plastic than in glass syringes, and O2 saturation always rose in plastic syringes. Differences between storage in plastic and glass syringes on PO2 change were greatest when initial blood PO2 was highest (mixture A). At the highest PO2, O2 exchange was faster in 3P than in 5P. The rise of PCO2 was just as fast in plastic as in glass syringes, but in both the rise in PCO2 was faster at a higher initial PCO2 (mixture B) than at lower initial PCO2 (mixtures B and C). Rates of PO2 and PCO2 change in matched samples were significantly faster in 3P than in 5P. Errors due to rises in PCO2 and PO2 cause additive errors in calculated A-aDO2, and when blood is stored in plastic syringes for >1 h significant errors result. Errors are greater in normoxic blood, in which estimated A-aDO2 decreased by >10 Torr after 6 h on ice in plastic syringes, than in hypoxic blood.

Background. Obesity is associated with an increased risk of bladder cancer recurrence. This study investigated the role of adipose tissue in bladder cancer progression. Methods. Gene expression profiling was performed on adipose tissues collected from normal weight (n=5), overweight (n=11), and obese (n=10) patients with invasive bladder cancer, and adipose stromal cells (ASCs) were obtained from two normal weight, two overweight, and two obese patients. Conditioned media (CM) was characterized and evaluated for its effects on the proliferation, migration, and invasive potential of T24 bladder cancer cells. Results. Expression profiling demonstrated depot-specific or body mass index-specific differences. Increased T24 cell migration was observed using CM harvested from all ASCs. ASC CM from an obese patient significantly increased T24 cell migration and invasion compared to ASC CM collected from normal weight and overweight patients. We identified abundant expression of CXCL1, PAI1, IL6, CX3CL1, and CCL2 in all CM. Exogenous treatment of T24 cells with PAI1, IL6, and CXCL1 enhanced migration. Depletion of CXCL1, PAI1, and IL6 in an obese patient ASC CM abrogated T24 migration. Conclusion. Factors secreted by adipose tissue influence the migration of bladder tumor cells and could play an active role in tumor progression.

The alkane elimination reaction between ZnMe2 and [(NMe3H)+(nido-C2B9H12)–] gives the macropolyhedral dimer [(nido-C2B9H11)ZnNMe3]2, containing an unprecedented planar diamond-shaped Zn2B2 ring at its core.

H1(R) is a Banach algebra which has better mapping properties under singular integrals than L1(R) . We show that its approximate identity sequences are unbounded by constructing one unbounded approximate identity sequence {vn}. We introduce a Banach algebra Q that properly lies between H1 and L1, and use it to show that c(1 + ln n) = ||vn||H1 = Cn1/2. We identify the maximal ideal space of H1 and give the appropriate version of Wiener's Tauberian theorem.

Generalizations of the Johnson parallelisms are given using an index m subgroup of a Pappian central collineation group. The parallelisms, called m-parallelisms, are constructed and the isomorphisms classes are discussed.

The collineation groups of even order translation planes which are cubic extensions of flag-transitive planes are determined.

Rhinoviruses (RVs) are the most common upper respiratory pathogens, inducing the majority of common colds worldwide. RV-related morbidity, although significant cumulatively, has been considered trivial for the individual patient. However, recent strong epidemiological associations of RVs with asthma exacerbations, including severe episodes requiring hospitalization, indicate that RV infections can result in serious disease. Current evidence supports the possibility that RVs infect the lower airways, inducing a local inflammatory response. Such evidence suggests that the role of RVs in other lower respiratory diseases, such as pneumonia, bronchitis, bronchiolitis and cystic fibrosis, should be re-examined with polymerase chain reaction-based methodologies, which are considerably more sensitive than traditional, cell culture-based techniques. The mechanisms through which RVs induce lower airway disease are studied to understand the relative contributions of the epithelial, neurogenic and immune components in the antiviral response, and to permit the design and implementation of specific treatments.

The main result is that if the translation complement of a translation plane of order q2 contains a group isomorphic to SL(2,q) and if the subgroups of order q are elations (shears), then the plane is Desarguesian. This generalizes earlier work of Walker, who assumed that the kernel of the plane contained GF(q).

This article discusses translation planes of dimension two and characteristic two. Let G be a subgroup of the linear translation complement of such a plane π. The nature of G and its possible action on π are investigated. This continues previous work of the authors. It is shown that no new groups occur.

Let π be a semi-transitive translation plane of even order with reference to the subplane π0. If π admits an affine elation fixing π0 for each axis in π0 and the order of π0 is not 2 or 8, then π is a Hall plane.

In this article we show the following: Let π be a translation plane of even order q2 that admits GL(2,q) as a collineation group. Then π is either Desarguesian, Hall or Ott-Schaeffer.

Let P be an affine translation plane of order q4 admitting a nonsolvable group G in its translation complement. If G fixes more than q+1 slopes, the structure of G is determined. In particular, if G is simple then q is even and G=L2(2s) for some integer s at least 2.