The design analyze of new hybrid drive concept

This paper presents the design method of hybrid drive system for the minibus with some limited conditions. The approach of design hybrid drive system is based on the dynamic modeling and simulation of the hybrid minibus with planetary gear system. The main target of the design is to obtain the optimal design with the proper hybrid drive configuration and control for a given set of design constraints. In oder to meet the design target, it's necessary to adjust some parameters such as mechanical ratios and parameters of battery pack as well as control by simulation. During simulation the transient operating process can be studied in details with the dynamic model in Matlab/Simulink. The control strategy can be optimized by running the simulation and monitoring the operation of each components: the operating area of internal combustion engine (ICE), fuel consumption (energy consumption), the power distribution, the torque and rotary speed of ICE and motor, the operating efficiency of motor, the alteration of battery state of charge (SOC), current and voltage.     

Brain potential and functional MRI evidence for how to handle two languages with one brain

Bilingual individuals need effective mechanisms to prevent interference from one language while processing material in the other. Here we show, using event-related brain potentials and functional magnetic resonance imaging (fMRI), that words from the non-target language are rejected at an early stage before semantic analysis in bilinguals. Bilingual Spanish/Catalan and monolingual Spanish subjects were instructed to press a button when presented with words in one language, while ignoring words in the other language and pseudowords. The brain potentials of bilingual subjects in response to words of the non-target language were not sensitive to word frequency, indicating that the meaning of non-target words was not accessed in bilinguals. The fMRI activation patterns of bilinguals included a number of areas previously implicated in phonological and pseudoword processing, suggesting that bilinguals use an indirect phonological access route to the lexicon of the target language to avoid interference.     

The power of images: mathematics and metaphysics in Hobbes's optics

This paper deals with Hobbes's theory of optical images, developed in his optical magnum opus, ‘A Minute or First Draught of the Optiques’ (1646), and published in abridged version in De homine (1658). The paper suggests that Hobbes's theory of vision and images serves him to ground his philosophy of man on his philosophy of body. Furthermore, since this part of Hobbes's work on optics is the most thoroughly geometrical, it reveals a good deal about the role of mathematics in Hobbes's philosophy. The paper points to some difficulties in the thesis of Shapin and Schaffer, who presented geometry as a ‘paradigm’ for Hobbes's natural philosophy. It will be argued here that Hobbes's application of geometry to optics was dictated by his metaphysical and epistemological principles, not by a blind belief in the power of geometry. Geometry supported causal explanation, and assisted reason in making sense of appearances by helping the philosopher understand the relationships between the world outside us and the images it produces in us. Finally the paper broadly suggests how Hobbes's theory of images may have triggered, by negative example, the flourishing of geometrical optics in Restoration England.     

Melanogenesis from tryptophan. Biogenetic experiments with harding-passey mouse melanoma

Riassunto Il triptofano¹⁴C-uniformemente marcato nell'anello benzenico e il triptofano marcato¹⁴C nel metilene sono incorporati in modo significativo nella melanina del melanoma di Harding-Passey del topo.5-ossitriptofano e 5-ossitriptamina non mostrano invece una significativa incorporazione nella stessa melanina. L'incorporazione ottenuta con il triptofano marcato sia nel nucleo che nel metilene è all'incirca uguale a quella ottenuta per somministrazione di tirosina-2-C¹⁴, per cui anche il triptofano deve essere considerato un precursore delle melanine.     

Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation

Activating B-RAF(V600E) (also known as BRAF) kinase mutations occur in ～7% of human malignancies and ～60% of melanomas. Early clinical experience with a novel class I RAF-selective inhibitor, PLX4032, demonstrated an unprecedented 80% anti-tumour response rate among patients with B-RAF(V600E)-positive melanomas, but acquired drug resistance frequently develops after initial responses. Hypotheses for mechanisms of acquired resistance to B-RAF inhibition include secondary mutations in B-RAF(V600E), MAPK reactivation, and activation of alternative survival pathways. Here we show that acquired resistance to PLX4032 develops by mutually exclusive PDGFRβ (also known as PDGFRB) upregulation or N-RAS (also known as NRAS) mutations but not through secondary mutations in B-RAF(V600E). We used PLX4032-resistant sub-lines artificially derived from B-RAF(V600E)-positive melanoma cell lines and validated key findings in PLX4032-resistant tumours and tumour-matched, short-term cultures from clinical trial patients. Induction of PDGFRβ RNA, protein and tyrosine phosphorylation emerged as a dominant feature of acquired PLX4032 resistance in a subset of melanoma sub-lines, patient-derived biopsies and short-term cultures. PDGFRβ-upregulated tumour cells have low activated RAS levels and, when treated with PLX4032, do not reactivate the MAPK pathway significantly. In another subset, high levels of activated N-RAS resulting from mutations lead to significant MAPK pathway reactivation upon PLX4032 treatment. Knockdown of PDGFRβ or N-RAS reduced growth of the respective PLX4032-resistant subsets. Overexpression of PDGFRβ or N-RAS(Q61K) conferred PLX4032 resistance to PLX4032-sensitive parental cell lines. Importantly, MAPK reactivation predicts MEK inhibitor sensitivity. Thus, melanomas escape B-RAF(V600E) targeting not through secondary B-RAF(V600E) mutations but via receptor tyrosine kinase (RTK)-mediated activation of alternative survival pathway(s) or activated RAS-mediated reactivation of the MAPK pathway, suggesting additional therapeutic strategies.     

North Pacific seasonality and the glaciation of North America 2.7 million years ago

In the context of gradual Cenozoic cooling, the timing of the onset of significant Northern Hemisphere glaciation 2.7 million years ago is consistent with Milankovitch's orbital theory, which posited that ice sheets grow when polar summertime insolation and temperature are low. However, the role of moisture supply in the initiation of large Northern Hemisphere ice sheets has remained unclear. The subarctic Pacific Ocean represents a significant source of water vapour to boreal North America, but it has been largely overlooked in efforts to explain Northern Hemisphere glaciation. Here we present alkenone unsaturation ratios and diatom oxygen isotope ratios from a sediment core in the western subarctic Pacific Ocean, indicating that 2.7 million years ago late-summer sea surface temperatures in this ocean region rose in response to an increase in stratification. At the same time, winter sea surface temperatures cooled, winter floating ice became more abundant and global climate descended into glacial conditions. We suggest that the observed summer warming extended into the autumn, providing water vapour to northern North America, where it precipitated and accumulated as snow, and thus allowed the initiation of Northern Hemisphere glaciation.     

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods-recursive partitioning and regression-to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; P(combined) = 2.01 x 10(-19) and 2.35 x 10(-13), respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes.     

Purification of diphtheria toxin by chromatography on Cibacron Blue-Sepharose

Diphtheria toxin binds to Cibacron Blue-Agarose and may be eluted by increasing the ionic strength of the elution buffer. Experiments using difference spectroscopy showed that the interaction between toxin and dye is ionic rather than hydrophobic, and therefore it is of a different nature with respect to that usually found in nucleotide-requiring enzymes.     

Large scale preparation of oxidized streptolysin O using molecular filtration

Summary Oxidized streptolysin O, suitable for the determination of antistreptolysin O in whole blood, has been prepared from crude broth culture ofS. pyogenes by molecular filtration using membranes with nominal mol. wt limit 10,000.