Biocatalytic preparation and absolute configuration of enantiomerically pure fungistatic anti-2-benzylindane derivatives. Study of the detoxification mechanism by Botrytis cinerea

Enantiomerically pure 2-benzylindane derivatives were prepared using biocatalytic methods and their absolute configuration determined. (1R,2S)-2-Benzylindan-1-ol ((1R,2S)-2) and (S)-2-benzylindan-1-one ((S)-3) were produced by fermenting baker’s yeast. Lipase-mediated esterifications and hydrolysis of the corresponding racemic substrates gave rise to the enantiopure compounds (1S,2R)-2-benzylindan-1-ol ((1S,2R)-2) and (1R,2S)-2-benzylindan-1-ol ((1R,2S)-2), respectively. The antifungal activity of these products against two strains of the plant pathogen Botrytis cinerea was tested. The metabolism of anti-(±)-2-benzylindan-1-ol (anti-(±)-2) by B. cinerea as part of the fungal detoxification mechanism is also described and revealed interesting differences in the genome of both strains

Mdm2 binding to a conformationally sensitive domain on p53 can be modulated by RNA

AbstractBiochemical characterisation of the interaction of mdm2 protein with p53 protein has demonstrated that full-length mdm2 does not bind stably to p53–DNA complexes, contrasting with C-terminal truncations of mdm2 which do bind stably to p53–DNA complexes. In addition, tetrameric forms of the p53His175 mutant protein in the PAb1620+ conformation are reduced in binding to mdm2 protein. These data suggest that the mdm2 binding site in the BOX-I domain of p53 becomes concealed when either p53 binds to DNA or when the core domain of p53 is unfolded by missense mutation. This further suggests that the C-terminus of mdm2 protein contains a negative regulatory domain that affects mdm2 protein binding to a second, conformationally sensitive interaction site in the core domain of p53. We investigated whether there was a second docking site on p53 for mdm2 protein by examining the interaction of full-length mdm2 with p53 lacking the BOX-I domain. Although mdm2 protein did bind very weakly to p53 protein lacking the BOX-I domain, addition of RNA activated mdm2 protein binding to this truncated form of p53. These data provide evidence for three previously undefined regulatory stages in the p53–mdm2 binding reaction: (1) conformational changes in p53 protein due to DNA binding or point mutation conceals a secondary docking site of mdm2 protein; (2) the C-terminus of mdm2 is the primary determinant which confers this property upon mdm2 protein; and (3) mdm2 protein binding to this secondary interaction site within p53 can be stabilised by RNA

Availability of pediatric and neonatal intensive care units in the city of São Paulo

OBJECTIVE: To describe the health care service provided in pediatric intensive care units in the city of São Paulo, by identifying and describing the units and analyzing their geographic distribution. METHODS: A descriptive cross-sectional study was carried out during a two-year period (August 2000 to July 2002). Data were collected through questionnaires answered by medical directors of each pediatric and neonatal intensive care unit. RESULTS: São Paulo is served by 107 pediatric and neonatal intensive care units, of which 85 (79.4%) completed and returned the questionnaire. We found a very unequal distribution of units as there were more units in places with the least pediatric population. Regarding to pediatric intensive care units specialization, 7% were pediatric, 41.2% were neonatal and 51.7% were mixed (pediatric and neonatal). Regarding hospital funds, 15.3% were associated with philanthropic institutions, 37.6% were private and 47% were public. A total of 1,067 beds were identified, of which 969 were active. The ratio bed/patient aged 0-14 was 1/2,728, varying from 1/604 at health districts - I to 1/6,812 at health districts - III. The units reported an average of 11.7 beds (2 to 60). The neonatal intensive care unit had a median of 16.9 beds per unit and pediatric intensive care units a median of 8.5 beds/unit. CONCLUSION: In São Paulo, we found an uneven distribution of pediatric and neonatal intensive care units among the health districts. There was also an uneven distribution between public and private units, and neonatal and pediatric ones. The current report is the first step in the effort to improve the quality of medical assistance in pediatric and neonatal intensive care units in São Paulo.OBJETIVO: Caracterizar a assistência de saúde prestada em tratamento intensivo pediátrico e neonatal no município de São Paulo através da identificação, descrição e distribuição geográfica das unidades. MÉTODOS: Estudo descritivo, tipo transversal, onde foram estudadas as unidades de terapia intensiva pediátrica e neonatal do município de São Paulo, no período de agosto de 2000 a julho de 2002. A coleta dos dados foi realizada por meio de questionário preenchido pelo coordenador médico de cada unidade. RESULTADOS: Foram listadas 107 unidades de terapia intensiva pediátricas e neonatais no município de São Paulo. Oitenta e cinco (79,4%) unidades forneceram os dados, constituindo a população de estudo. Observou-se maior número de unidades de terapia intensiva em Núcleos Regionais de Saúde com menor população pediátrica. Quanto à faixa etária, 7% eram exclusivamente pediátricas, 41,2% neonatais, e 51,7% mistas. Em relação ao mantenedor: 47% eram públicas, 37,6% privadas, e 15,3% filantrópicas. Identificamos 1.067 leitos, estando 969 em atividade. A razão leito/paciente de 0 a 14 anos foi de 1:2.728, variando de 1:604 (Núcleo Regional de Saúde - I) a 1:6.812 (Núcleo Regional de Saúde - III). O número de leitos por unidade variou de 2 a 60, com média de 11,7 (unidades de terapia intensiva neonatais: 16,9; mistas: 8,5). CONCLUSÃO: No município de São Paulo, observou-se uma distribuição desproporcional das unidades de terapia intensiva pediátrica e neonatal entre os cinco Núcleos Regionais de Saúde. Houve também uma distribuição desproporcional entre unidades de terapia intensiva públicas e privadas e entre neonatais e pediátricas. Esse estudo foi o primeiro esforço na busca por melhor qualidade na assistência intensiva pediátrica e neonatal no município de São Paulo.Universidade de São Paulo Faculdade de MedicinaUniversidade Federal de São Paulo (UNIFESP) Departamento de PediatriaUniversidade de São Paulo Hospital Universitário Unidade de Terapia Intensiva PediátricaUNIFESP, Depto. de PediatriaSciEL

The effects of an intronic polymorphism in TOMM40 and APOE genotypes in sporadic inclusion body myositis.

A previous study showed that, in carriers of the apolipoprotein E (APOE) genotype ε3/ε3 or ε3/ε4, the presence of a very long (VL) polyT repeat allele in "translocase of outer mitochondrial membrane 40" (TOMM40) was less frequent in patients with sporadic inclusion body myositis (sIBM) compared with controls and associated with a later age of sIBM symptom onset, suggesting a protective effect of this haplotype. To further investigate the influence of these genetic factors in sIBM, we analyzed a large sIBM cohort of 158 cases as part of an International sIBM Genetics Study. No significant association was found between APOE or TOMM40 genotypes and the risk of developing sIBM. We found that the presence of at least 1 VL polyT repeat allele in TOMM40 was significantly associated with about 4 years later onset of sIBM symptoms. The age of onset was delayed by 5 years when the patients were also carriers of the APOE genotype ε3/ε3. In addition, males were likely to have a later age of onset than females. Therefore, the TOMM40 VL polyT repeat, although not influencing disease susceptibility, has a disease-modifying effect on sIBM, which can be enhanced by the APOE genotype ε3/ε3

70.3: Current‐Scaling a‐Si:H TFT Pixel Electrode Circuit for AM‐OLEDs

We fabricated and characterized the amorphous silicon thin‐film transistor (a‐Si:H TFT) pixel electrode circuit with currentscaling function that can be used for active‐matrix organic lightemitting displays (AM‐OLEDs). As expected from previously reported simulation results, fabricated circuit showed an acceptable current‐scaling performance for a high‐resolution AM‐OLED based on a‐Si:H TFTs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92085/1/1.2451422.pd

Stellar spectroscopy: Fermions and holographic Lifshitz criticality

Electron stars are fluids of charged fermions in Anti-de Sitter spacetime. They are candidate holographic duals for gauge theories at finite charge density and exhibit emergent Lifshitz scaling at low energies. This paper computes in detail the field theory Green's function G^R(w,k) of the gauge-invariant fermionic operators making up the star. The Green's function contains a large number of closely spaced Fermi surfaces, the volumes of which add up to the total charge density in accordance with the Luttinger count. Excitations of the Fermi surfaces are long lived for w <~ k^z. Beyond w ~ k^z the fermionic quasiparticles dissipate strongly into the critical Lifshitz sector. Fermions near this critical dispersion relation give interesting contributions to the optical conductivity.Comment: 38 pages + appendices. 9 figure

Strings on Bubbling Geometries

We study gauge theory operators which take the form of a product of a trace with a Schur polynomial, and their string theory duals. These states represent strings excited on bubbling AdS geometries which are dual to the Schur polynomials. These geometries generically take the form of multiple annuli in the phase space plane. We study the coherent state wavefunction of the lattice, which labels the trace part of the operator, for a general Young tableau and their dual description on the droplet plane with a general concentric ring pattern. In addition we identify a density matrix over the coherent states on all the geometries within a fixed constraint. This density matrix may be used to calculate the entropy of a given ensemble of operators. We finally recover the BMN string spectrum along the geodesic near any circle from the ansatz of the coherent state wavefunction.Comment: 41 pages, 12 figures, published version in JHE

The impact of low erythrocyte density in human blood on the fitness and energetic reserves of the African malaria vector Anopheles gambiae

Background Anaemia is a common health problem in the developing world. This condition is characterized by a reduction in erythrocyte density, primarily from malnutrition and/or infectious diseases such as malaria. As red blood cells are the primary source of protein for haematophagous mosquitoes, any reduction could impede the ability of mosquito vectors to transmit malaria by influencing their fitness or that of the parasites they transmit. The aim of this study was to determine the impact of differences in the density of red blood cells in human blood on malaria vector (Anopheles gambiae sensu stricto) fitness. The hypotheses tested are that mosquito vector energetic reserves and fitness are negatively influenced by reductions in the red cell density of host human blood meals commensurate with those expected from severe anaemia. Methods Mosquitoes (An. gambiae s.s.) were offered blood meals of different packed cell volume(PCV) of human blood consistent with those arising from severe anaemia (15%) and normalPCV (50%). Associations between mosquito energetic reserves (lipid, glucose and glycogen)and fitness measures (reproduction and survival) and blood meal PCV were investigated. Results The amount of protein that malaria vectors acquired from blood feeding (indexed by haematin excretion) was significantly reduced at low blood PCV. However, mosquitoes feeding on blood of low PCV had the same oviposition rates as those feeding on blood of normal PCV, and showed an increase in egg production of around 15%. The long-term survival of An. gambiae s.s was reduced after feeding on low PCV blood, but PCV had no significant impact on the proportion of mosquitoes surviving through the minimal period required to develop and transmit malaria parasites (estimated as 14 days post-blood feeding). The impact of blood PCV on the energetic reserves of mosquitoes was relatively minor. Conclusions These results suggest that feeding on human hosts whose PCV has been depleted due to severe anaemia does not significantly reduce the fitness or transmission potential of malaria vectors, and indicates that mosquitoes may be able exploit resources for reproduction more efficiently from blood of low rather than normal PCV

Effects of Age, Race, and Ethnicity on the Optic Nerve and Peripapillary Region Using Spectral-Domain OCT 3D Volume Scans

Purpose: To evaluate the effects of age, race, and ethnicity on the optic nerve and peripapillary retina using spectral-domain optical coherence tomography (SD-OCT) three-dimensional (3D) volume scans in normal subjects. Methods: This is a cross-sectional study performed at a single institution in Boston. All patients received retinal nerve fiber layer (RNFL) scans and an optic nerve 3D volume scan. The SD-OCT software calculated peripapillary RNFL thickness, retinal thickness (RT), and retinal volume (RV). Custom-designed software calculated neuroretinal rim minimum distance band (MDB) thickness and area. Results: There were 272 normal subjects, including 175 whites, 40 blacks, 40 Asians, and 17 Hispanics. Rates of age-related decline were 2.3%, 2.0%, 1.7%, 3.3%, and 4.3% per decade for RNFL, RT, RV, MDB neuroretinal rim thickness, and MDB area, respectively. The RNFL was most affected by racial and ethnic variations, with Asians having thicker global, superior, and inferior RNFL, Hispanics having thicker inferior RNFL, and blacks having thinner temporal RNFL, compared to whites. For MDB thickness and area, Asians had smaller nasal values and blacks had smaller temporal values. Peripapillary RT and RV parameters were not influenced by race and ethnicity. Conclusions: All of the parameters exhibited age-related declines. RNFL, MDB thickness, and MDB area demonstrated racial and ethnic variations, while peripapillary RT and RV did not. Translational Relevance: This study demonstrates that both normal aging and ethnicity affect several novel 3D OCT parameters used to diagnose and monitor glaucoma (i.e., RT, RV, and MDB), and this should be factored in when making clinical decisions based on these parameters

Effects of Age, Race, and Ethnicity on the Optic Nerve and Peripapillary Region Using Spectral-Domain OCT 3D Volume Scans

Purpose: To evaluate the effects of age, race, and ethnicity on the optic nerve and peripapillary retina using spectral-domain optical coherence tomography (SD-OCT) three-dimensional (3D) volume scans in normal subjects. Methods: This is a cross-sectional study performed at a single institution in Boston. All patients received retinal nerve fiber layer (RNFL) scans and an optic nerve 3D volume scan. The SD-OCT software calculated peripapillary RNFL thickness, retinal thickness (RT), and retinal volume (RV). Custom-designed software calculated neuroretinal rim minimum distance band (MDB) thickness and area. Results: There were 272 normal subjects, including 175 whites, 40 blacks, 40 Asians, and 17 Hispanics. Rates of age-related decline were 2.3%, 2.0%, 1.7%, 3.3%, and 4.3% per decade for RNFL, RT, RV, MDB neuroretinal rim thickness, and MDB area, respectively. The RNFL was most affected by racial and ethnic variations, with Asians having thicker global, superior, and inferior RNFL, Hispanics having thicker inferior RNFL, and blacks having thinner temporal RNFL, compared to whites. For MDB thickness and area, Asians had smaller nasal values and blacks had smaller temporal values. Peripapillary RT and RV parameters were not influenced by race and ethnicity. Conclusions: All of the parameters exhibited age-related declines. RNFL, MDB thickness, and MDB area demonstrated racial and ethnic variations, while peripapillary RT and RV did not. Translational Relevance: This study demonstrates that both normal aging and ethnicity affect several novel 3D OCT parameters used to diagnose and monitor glaucoma (i.e., RT, RV, and MDB), and this should be factored in when making clinical decisions based on these parameters