Prof Les Carr interviews Bebo White

Prof Les Carr interviews Bebo White about the Early Web and the Future Web – the Internet of Things

New radiocarbon accelerator dates on artefacts from the early Mesolithic site of Star Carr, North Yorkshire

For the well-known early Mesolithic site of Star Carr, dating of organic artefacts by accelerator mass spectrometry (AMS) has been hampered by treatment of bone and antler recovered during the original excavations with preservatives. Some, untreated, artefacts were, however, collected after Clark's excavation in 1950. Four of these artefacts were AMS dated in 1995, but two of the dates were significantly younger than the others, and were questionable due to their low collagen yields. These suspect samples have now been re-analysed, demonstrating that all four artefacts are of similar date. The significance of these dates for the chronology of Star Carr is discussed.

Mapping antimalarial pharmacophores as a useful tool for the rapid discovery of drugs effective in vivo: design, construction, characterization, and pharmacology of metaquine

Resistant strains of Plasmodium falciparum and the unavailability of useful antimalarial vaccines reinforce the need to develop new efficacious antimalarials. This study details a pharmacophore model that has been used to identify a potent, soluble, orally bioavailable antimalarial bisquinoline, metaquine (N,N'-bis(7-chloroquinolin-4-yl)benzene-1,3-diamine) (dihydrochloride), which is active against Plasmodium berghei in vivo (oral ID50 of 25 mu mol/kg) and multidrug-resistant Plasmodium falciparum K1 in vitro (0.17 mu M). Metaquine shows strong affinity for the putative antimalarial receptor, heme at pH 7.4 in aqueous DMSO. Both crystallographic analyses and quantum mechanical calculations (HF/6-31+G*) reveal important regions of protonation and bonding thought to persist at parasitic vacuolar pH concordant with our receptor model. Formation of drug-heme adduct in solution was confirmed using high-resolution positive ion electrospray mass spectrometry. Metaquine showed strong binding with the receptor in a 1: 1 ratio (log K = 5.7 +/- 0.1) that was predicted by molecular mechanics calculations. This study illustrates a rational multidisciplinary approach for the development of new 4-aminoquinoline antimalarials, with efficacy superior to chloroquine, based on the use of a pharmacophore model.

Stanley Lloyd Miller e a origem da vida: uma possibilidade para o estudo da natureza da ciência

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Qualitative analysis by online nuclear magnetic resonance using Carr-Purcell-Meiboom-Gill sequence with low refocusing flip angles

The Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence has been used in many applications of magnetic resonance imaging (MRI) and low-resolution NMR (LRNMR) spectroscopy. Recently. CPMG was used in online LRNMR measurements that use long RF pulse trains, causing an increase in probe temperature and, therefore, tuning and matching maladjustments. To minimize this problem, the use of a low-power CPMG sequence based on low refocusing pulse flip angles (LRFA) was studied experimentally and theoretically. This approach has been used in several MRI protocols to reduce incident RF power and meet the specific absorption rate. The results for CPMG with LRFA of 3 pi/4 (CPMG(135)), pi/2 (CPMG(90)) and pi/4 (CPMG(45)) were compared with conventional CPMG with refocusing pi pulses. For a homogeneous field, with linewidth equal to Delta nu = 15 Hz, the refocusing flip angles can be as low as pi/4 to obtain the transverse relaxation time (T(2)) value with errors below 5%. For a less homogeneous magnetic field. Delta nu = 100 Hz, the choice of the LRFA has to take into account the reduction in the intensity of the CPMG signal and the increase in the time constant of the CPMG decay that also becomes dependent on longitudinal relaxation time (T(1)). We have compared the T(2) values measured by conventional CPMG and CPMG(90) for 30 oilseed species, and a good correlation coefficient, r = 0.98, was obtained. Therefore, for oilseeds, the T(2) measurements performed with pi/2 refocusing pulses (CPMG(90)), with the same pulse width of conventional CPMG, use only 25% of the RF power. This reduces the heating problem in the probe and reduces the power deposition in the samples. (C) 2011 Elsevier B.V. All rights reserved.

Use of Carr-Purcell pulse sequence with low refocusing flip angle to measure T-1 and T-2 in a single experiment

The Carr-Purcell pulse sequence, with low refocusing flip angle, produces echoes midway between refocusing pulses that decay to a minimum value dependent on T*(2). When the refocusing flip angle was pi/2 (CP90) and tau > T*(2), the signal after the minimum value, increased to reach a steady-state free precession regime (SSFP), composed of a free induction decay signal after each pulse and an echo, before the next pulse. When tau < T*(2), the signal increased from the minimum value to the steady-state regime with a time constant (T*) = 2T(1)T(2)/(T-1 + T-2). identical to the time constant observed in the SSFP sequence, known as the continuous wave free precession (CWFP). The steady-state amplitude obtained with M-cp90 = M0T2/(T-1+T-2) was identical to CWFP. Therefore, this sequence was named CP-CWFP because it is a Carr-Purcell sequence that produces results similar to the CWFP. However, CP-CWFP is a better sequence for measuring the longitudinal and transverse relaxation times in single scan, when the sample exhibits T-1 similar to T-2. Therefore, this sequence can be a useful method in time domain NMR and can be widely used in the agriculture, food and petrochemical industries because those samples tend to have similar relaxation times in low magnetic fields. (C) 2011 Elsevier Inc. All rights reserved.

Quatro Desenhos de Frank Lloyd Wright

O objetivo deste trabalho é discutir aspectos do processo de projeto e sua representação gráfica, num momento em que softwares de projeto 3D vem se tornando hegemônicos na prática do arquiteto e no ensino de arquitetura, em contraponto às práticas de desenho em prancheta. Os motivos e circunstâncias não são objeto do trabalho, cujo foco está numa prática de projeto e representação gráfica 2D, mas que tem muito a contribuir para o debate do quadro acima: os desenhos de projeto de Frank Lloyd Wright. Casos de estudo: quatro pranchas desenhadas por FLLW. É importante notar que, no vasto quadro da historiografia wrightiana, análises e interpretações originais, pioneiras, da arquitetura vem surgindo nas últimas décadas, mas ainda há poucos textos sobre desenhos e representação gráfica do arquiteto. Este constitui uma primeira aproximação do autor acerca de tema que oferece abrangente potencial. São exemplos em que, na relação imagem-objeto, a representação bidimensional constrói o projeto tridimensional. A arquitetura emerge como experimentação sem cair na especulação formal. Demonstram uma prática mais lenta, reflexiva e laboriosa do que a oferecida pelos software 3D atuais – mas onde cada traço, textura e grafismo implica um significado de espaço e materialidade.