苏丹被动裂谷盆地的油气成藏机理和成藏模式

The research area of this paper covers the maximum exploration projects of CNPC, including Blocks 1/2/4 and Block 6 of the Muglad basin and the Melut basin in Bocks 3/7 in Sudan. Based on the study of the evolution history of the Central African Shear Zone (CASZ), structural styles and filling characteristics of the rift basins, it is put forward that the rift basins in Sudan are typical passive rift basins undergoing the strike-slip, extension, compression and inversion since the Cretaceous. The three-stage rift basins overlapped obliquely. The extension and rifting during the Early Cretaceous is 50-70% of the total extension. The features of the passive rift basins decided that there is a single sedimentary cycle and one set of active source rocks within the middle. Influenced by the three-stage rifting and low thermal gradient, hydrocarbon generation and charging took place very late, and the oil pool formation mechanism is very unique from the Lower Cretaceous rift sequences to the Paleogene. The reservoir-seal assemblages are very complicated in time and space. The sealing capacity of cap rocks was controlled by the CASZ. In general the oils become heavier towards the CASZ and lighter far away. The oil biodegradation is the reason causing the high total acid number. The determination of effective reservoir depth ensures that all discovered fields up to now are high-production fields. The propagation and growth of boundary faults in the rift basins can be divided into a simple fault propagation pattern and a fault growth-linkage pattern. It is firstly found that the linkage of boundary fault segments controls the formation of petroleum systems. Three methods have been established to outline petroleum systems. And a new classification scheme of rift-type petroleum system has been put forward: pre-rift, syn-rift (including passive and active) and post-rift petroleum systems. This scheme will be very important for the further exploration of rift basins. This paper firstly established the formation models of oil pools for the passive rift basins in Sudan: the coupling of accommodation zones and main plays for the formation of giant fields. The overlapping of late rifting broke the anticlines to be several fault-blocks. This process determined that anti-fault blocks are the main traptypes in the cretaceous sequences and anticlines in the Paleogene. This can explain why the traptypes are different between the Muglad and Mefut basins, and will provide theoretic guidance for the exploration strategy. The established formation mechanism and models in this paper have had great potential guidance and promotion for the exploration in Sudan, and resulted in significant economic and social benefit. A giant field of 500 million tons oil in place was found 2003. The cost in Blocks 3/7 is only 0.25

东营凹陷沙三中亚段湖相浊积岩储层特征及油气成藏规律研究

Turbidity sandstone reservoirs have been an important field of hydrocarbon exploration and development in the basins all over the world, as well as in China. Lithologic pools are composed of turbidity sandstones and other sandstones are frequently found in the Jiyang Depression that is a Mesozoic-Cenozoic non-marine oil-bearing basin. The Dongying Sag lies in the sedimentary center of the basin. The subtle traps with turbidity reservoirs are generally difficult to be predicted and described by using current techniques. The studies on turbidity reservoirs plays thus an important theoretical and theoretical practical role in exploration and development in the Jiyang Depression. The attention is, in this thesis, focused on the petrologic properties and oil accumulating behaviors in lake turbidity sedimentary systems in the middle part of the third section of Shahejie Formation in the Dongying Sag, especially in Dongxin area, which lies on the central uplift of the Sag. The paper has disclosed the origin types of turbidity sandstones, distribution pattern and controlling factors of turbidity sandstones, and set up hydrocarbon accumulation patterns of the middle part of the third section of Shahejie Formation in Dongxin, based on nonmarine high resolution sequence stratigraphy, event sedimentology and new theories of hydrocarbon forming. By studying prediction method and technology of turbidity sandstone reservoirs, using precise geological model developing, new techniques of high resolution seismic inversion constrained by logging, the paper has forecast low permeability turbidity sandstone reservoirs and pointed out advantage exploration aims to progressive exploration and development. The paper has obtained mainly many productions and acknowledges as follows: 1.Turbidity sandstone reservoirs of the third section of Shahejie Formationin Dongying Sag are formed in such specifical geological background as rift and extension of basin. The inherited Dongying delta and transgression make up many turbidity distribution areas by overlaying and joining together. The hydrocarbon migrates from depression area to adjacent turbidity sandstone continuously. Accumulation area which is sufficient in oil is formed. 2.The paper has confirmed distinguishable sign of sequence boundary , established stratigraphic framework of Dongying Sag and realized isotime stratigraphic correlation. Es3 of Dongying delta is divided into eleven stages. Among them, the second period of the lower section in Es3, the sixth period of the middle section in Es3, the third period of the upper section in Es3 correspond to eleven sedimentary isotime surface in seismic profile, namely Es3 is classified into eleven Formations. 3.According to such the features of turbidity sandstone as deep in burial, small in area, strong in subtle property, overlaying and joining together and occurring in groups, management through fault and space variations of restriction quantum are realized and the forecast precision of turbidity sandstone by using precise geological model developing, new techniques of high resolution seismic inversion constrained by logging, based on the analysis of all kinds of interwell seismic inversion techniques. 4.According to the features of low permeable turbidity sandstone reservoirs, new method of log interpretation model is put forward. At the same time, distinguish technology of familiar low resistivity oil layer in the turbidity sandstone reservoirs is studied based on petrophysical laboratory work and "four properties" interrelationship between lithological physical Jogging and bearing hydrocarbon properties. Log interpretation model and reservoir index interpretation model of low resistivity oil layer are set up. So the log interpretation precision is improved. 5.The evolution law and its difference of the turbidity sandstone are embodies as follows: the source of sediments come from the south and east of the study area in the middle period of Es3. East source of sediments is pushed from west to east. However, the south source supply of sediments in the early and middle period of Es3 is in full, especially in Es3. subsequently, the supply is decreased gradually. Turbidity fan moves back toward the south and the size of fan is minished accordingly. The characteristic of turbidity sandstone in Dongying Sag is different in different structural positions. Dongxin in the middle-east of the central lift and Niuzhuang Sag He in Dongying delta front and prodelta deep lake subfacies. Although the turbidity sandstone of the two areas root in the Dongying delta sedimentary system, the sand body has different remarkably characteristic. 6.The sedimentary model of the turbiditys in study area have three types as follows: (1) collapse turbidity fan in respect of delta; (2) fault trench turbidity fan; (3) other types of microturbidity sandstone. Middle fan and outer fan, can be found mainly in sublacustrine fan. Middle fan includes braided channel microfacies, central microfacies and braided interchannel microfacies, which is main prospecting oil-bearing subfacies. The middle section of the third section of Shahejie Formation in study area (for example the central lift) can be divided into middle-lower and upper part. The middle-lower part is characteristic of turbidity fan. The upper part is sedimented mainly by delta-collapse fan. 7.The turbidity reservoirs of the middle part of the third section of Shahejie Formation in study area characterize by low maturity both in component and texture, strong in diagenesis and low in permeability. The reservoir can be classified into four types. Type III is the body of reservoir and comprises two types of H a and HI b. M a belongs to middle porosity - low permeability reservoir and distributes in the central lift. Hlb belongs to low porosity - low permeability and distributes in Haojia region. 8.A11 single sand body of lens turbidity reservoir of the middle part of the third section of Shahejie Formation in study area are surrounded by thick dark source rocks. The oil-water system is complex and behaves that every sandstone is single seal unit. The water body is 1/3-1-5 of the sand body. The edge water is not active. The gas exists in the top of reservoir in the form of mixed gas. For far-range turbidity fan with big scale channel, the area and volume of sand body is large and the gap is big in oil packing degree. There are lots of edge water and bottom water, and the latter increases rapidly during the course of development. 9.By exerting the modern hydrocarbon forming theories, the third section of Shahejie Formation in study area belongs to abnormally pressured fluid compartment. The lithological reservoir of the third section of Shahejie Formation is formed in the compartment. The reservoir-formed dynamic system belongs to lower self-source enclosed type. The result and the practice indicate that the form and accumulation of lithological oil reservoirs are controlled by the temperature and pressure of stratum, microfacies, thickness of sand body, fault and reservoir heterogeneity. 10. Based on studies above, the emphases focus on in south and north part of Dongying structure, west Dongxin region and south part Xinzhen structure in the application of production. The practice proves that the turbidity sandstone reservoirs in Ying 11 block and the fault-lithological reservoirs in Xin 133 block have been obtained significant breakthrough. The next target is still sandstone groups of the third section of Shahejie Formation in the bordering areas of Dongxin region for instance Xin 149 area, He 89 area, Ying 8 area etc.

利用宽频带台阵资料研究华北地区地壳及上地幔间断面结构

Intense tectonic renovation has occurred in the eastern continent of china since Mesozoic, as evidenced by the high heat flow, widespread magma extrusion and volcanic activities, and development of large sedimentary basins. To explain the cause and mechanism for the tectonic process in this period, some researchers have put forward various models, such as mantle plume, subduction of the Pacific slab, Yangtze Block-North China Block collision, etc. Their seismological evidence, however, is still scarce..During the period from 2000 to 2003, large temporary seismic arrays were established in North China by the Institute of the Geology and Geophysics, Chinese Academy of Sciences. Total 129 portable seismic stations were linearly emplaced across the western and eastern boundaries of the Bohai Bay Basin, and accumulated a large amount of high-quality data. Moreover, abundant data were also collected at the capital digital seismic network established in the ninth five-year period of national economic and social development. These provide an unprecedented opportunity for us to study the deep structure and associated geodynamic mechanism of lithospheric processes in North China using seismological techniques.Seismology is a kind of observation-based science. The development of seismic observations greatly promotes the improvement of seismologic theory and methodology. At the beginning of this thesis, I review the history of seismic observation progress, and present some routine processing techniques used in the array seismology. I also introduce two popular seismic imaging methods (receiver function method and seismic tomography).Receiver function method has been widely used to study the crustal and upper mantle structures, and many relevant research results have been published. In this thesis I elaborate the theory of this method, including the basic concept of receiver functions and the methodology for data pre-processing, stacking and migration. I also address some problems often encountered in practical applications of receiver function imaging.By using the teleseismic data collected at the temporary seismic arrays in North China, in particular, the traveltime information of P-to-S conversion and multiple reverberations of the Moho discontinuity, I obtain the distributions of the crustal thickness and the poisson ratio at the northwest boundary area of the Bohai Bay Basin and discuss the geological implications of the results.Through detailed intestigations on the crustal structural feature around the middle part of the Tanlu fault, considerable disparity in poisson ratios is found in the western and eastern sides of the Tanlu fault. Moreover, an obvious Moho offset is coincidently observed at the same surface location. A reasonable density model for the Tanlu fault area is also derived by simulating the observed gravity variations. Both receiver function study and gravity anomaly modeling suggest that the crustal difference between the western and eastern sides of the Tanlu fault is mainly resulted from their different compositions.With common conversion point imaging of receiver functions, I estimate the depths of the upper and lower boundaries of the mantle transition zone, i.e., the 410 and 660 km discontinuities, beneath most part of the North China continent The thickness of the transition zone (TTZ) in the study area is calculated by subtracting the depth of .410 km discontinuity from that of the 660km discontinuity. The resultant TTZ is 10-15 km larger in the east than in the west of the study area. Phase transitions at the 410 km and the 660 km discontinuities are known to have different Clapeyron slopes. Therefore, the TTZ is sensitive to the temperature changes in the transition zone. Previous studies have shown that the TTZ would be smaller in the mantle plume areas and become larger when the remnants of subducted slabs are present The hypothesis of mantle plume cannot give a reasonable interpretation to the observed TTZ beneath North China, Instead, the receiver function imaging results favor a dynamic model that correlates the thermal structure of the mantle transition zone and associated upper mantle dynamics of North China to the Pacific plate subduction process.

地震偏移宽角吸收边界条件和Toeplitz矩阵反演中的边界效应研究

The content of this paper is based on the research work while the author took part in the key project of NSFC and the key project of Knowledge Innovation of CAS. The whole paper is expanded by introduction of the inevitable boundary problem during seismic migration and inversion. Boundary problem is a popular issue in seismic data processing. At the presence of artificial boundary, reflected wave which does not exist in reality comes to presence when the incident seismic wave arrives at the artificial boundary. That will interfere the propagation of seismic wave and cause alias information on the processed profile. Furthermore, the quality of the whole seismic profile will decrease and the subsequent work will fail.This paper has also made a review on the development of seismic migration, expatiated temporary seismic migration status and predicted the possible break through. Aiming at the absorbing boundary problem in migration, we have deduced the wide angle absorbing boundary condition and made a compare with the boundary effect of Toepiitz matrix fast approximate computation.During the process of fast approximate inversion computation of Toepiitz system, we have introduced the pre-conditioned conjugate gradient method employing co circulant extension to construct pre-conditioned matrix. Especially, employment of combined preconditioner will reduce the boundary effect during computation.Comparing the boundary problem in seismic migration with that in Toepiitz matrix inversion we find that the change of boundary condition will lead to the change of coefficient matrix eigenvalues and the change of coefficient matrix eigenvalues will cause boundary effect. In this paper, the author has made an qualitative analysis of the relationship between the coefficient matrix eigenvalues and the boundary effect. Quantitative analysis is worthy of further research.

Synthesis of a group of diosgenyl saponins with combined use of glycosyl trichloroacetimidate and thioglycoside donors

With the combined use of glycosyl trichloroacetimidates and thioglycosides, a group of natural diosgenyl saponins (1-6) are efficiently synthesized, in either a stepwise or a 'one-pot' manner. The trichloroacetimidate is employed as an efficient temporary hydroxy protecting group in glycosylation with the glycosyl trichloroacetimidate. The intermolecular alkylthio-group transfer is demonstrated to be a common side-reaction during glycosylation with thioglycosides.

RABBIT: A Compiler for SCHEME

We have developed a compiler for the lexically-scoped dialect of LISP known as SCHEME. The compiler knows relatively little about specific data manipulation primitives such as arithmetic operators, but concentrates on general issues of environment and control. Rather than having specialized knowledge about a large variety of control and environment constructs, the compiler handles only a small basis set which reflects the semantics of lambda-calculus. All of the traditional imperative constructs, such as sequencing, assignment, looping, GOTO, as well as many standard LISP constructs such as AND, OR, and COND, are expressed in macros in terms of the applicative basis set. A small number of optimization techniques, coupled with the treatment of function calls as GOTO statements, serve to produce code as good as that produced by more traditional compilers. The macro approach enables speedy implementation of new constructs as desired without sacrificing efficiency in the generated code. A fair amount of analysis is devoted to determining whether environments may be stack-allocated or must be heap-allocated. Heap-allocated environments are necessary in general because SCHEME (unlike Algol 60 and Algol 68, for example) allows procedures with free lexically scoped variables to be returned as the values of other procedures; the Algol stack-allocation environment strategy does not suffice. The methods used here indicate that a heap-allocating generalization of the "display" technique leads to an efficient implementation of such "upward funargs". Moreover, compile-time optimization and analysis can eliminate many "funargs" entirely, and so far fewer environment structures need be allocated at run time than might be expected. A subset of SCHEME (rather than triples, for example) serves as the representation intermediate between the optimized SCHEME code and the final output code; code is expressed in this subset in the so-called continuation-passing style. As a subset of SCHEME, it enjoys the same theoretical properties; one could even apply the same optimizer used on the input code to the intermediate code. However, the subset is so chosen that all temporary quantities are made manifest as variables, and no control stack is needed to evaluate it. As a result, this apparently applicative representation admits an imperative interpretation which permits easy transcription to final imperative machine code. These qualities suggest that an applicative language like SCHEME is a better candidate for an UNCOL than the more imperative candidates proposed to date.

A Planning System for Robot Construction Tasks

This paper describes BUILD, a computer program which generates plans for building specified structures out of simple objects such as toy blocks. A powerful heuristic control structure enables BUILD to use a number of sophisticated construction techniques in its plans. Among these are the incorporation of pre-existing structure into the final design, pre-assembly of movable sub-structures on the table, and use of the extra blocks as temporary supports and counterweights in the course of construction. BUILD does its planning in a modeled 3-space in which blocks of various shapes and sizes can be represented in any orientation and location. The modeling system can maintain several world models at once, and contains modules for displaying states, testing them for inter-object contact and collision, and for checking the stability of complex structures involving frictional forces. Various alternative approaches are discussed, and suggestions are included for the extension of BUILD-like systems to other domains. Also discussed are the merits of BUILD's implementation language, CONNIVER, for this type of problem solving.

Supressão do crescimento de plantas voluntárias de soja na cultura do girassol.

RESUMO: A necessidade de controle adequado de plantas voluntárias de soja (Glycine max) tem se intensificado nos últimos anos em função da incidência de doenças da soja, principalmente a ferrugem asiática ( Phakopsora pachyrhizi). Além disso, a competição imposta por essas plantas pode causar perdas de produtividade em culturas implantadas na entressafra. Dois experimentos foram conduzidos em condições de campo no município de Rio Verde, Goiás, a fim de avaliar o controle de plantas voluntárias de soja infestantes da cultura do girassol (Helianthus annuus), semeado na época de safrinha. O delineamento experimental foi em blocos casualizados, com quatro repetições. Os tratamentos aplicados no experimento 1 foram a testemunha capinada, a testemunha sem capina, sulfentrazone 25 g i.a. ha-1, sulfentrazone 50 g i.a. ha -1, sulfentrazone 100 g i.a. ha-1 e sulfentrazone 150 g i.a. ha-1. No experimento 2, foram aplicados os mesmos tratamentos mencionados e acrescentadas as doses de 200 g i.a. ha-1 e 250 g i.a. ha-1 do mesmo herbicida. O sulfentrazone não proporciona morte completa das plantas voluntárias de soja. No entanto, há uma interrupção temporária do crescimento da soja permitindo o arranque inicial da cultura de girassol. As doses de sulfentrazone que variaram de 114,2 a 158,8 g i.a. ha-1 proporcionaram os maiores rendimentos de girassol, evitando a competição das plantas voluntárias de soja com essa cultura. ABSTRACT: The control of volunteer soybean plants (Glycine max ) has intensified in recent years in function of the increasing incidence of soybean diseases mainly the Asian soybean rust (Phakopsora pachyrhizi). Moreover, the competition of volunteer soybean plants can cause yield losses in successive crops. Two experiments were conducted under field conditions in Rio Verde, Goiás State, Brazil, in order to evaluate the control of volunteer soybean plants in sunflower (Helianthus annuus). The experimental design was a randomized complete block, with four replications. Treatments applied on experiment 1 were: hoed check; unhoed check, sulfentrazone 25 g ai ha-1, sulfentrazone 50 g ai ha-1, sulfentrazone 100 g ai ha-1, sulfentrazone 150 g ai ha-1. The treatments applied on experiment 2 were the same doses described on experiment 1 plus sulfentrazone 200 g ai ha-1 and 250 g ai ha-1. The sulfentrazone is unable to completely kill the volunteer soybean plants. However, there is a temporary stoppage of soybean growth enabling the initial startup of the sunflower plants. Doses ranging from 114.2 to 158.8 g ai ha-1 provided the highest sunflower yield, avoiding the competition of the volunteer soybean plants.

Kształtowanie systemu politycznego Kazachstanu w latach 1991-2000. Kontekst historyczno-kulturowy

Wydział Historyczny

Communicable Memory and Lazy Barriers for Bulk Synchronous Parallelism in BSPk

Communication and synchronization stand as the dual bottlenecks in the performance of parallel systems, and especially those that attempt to alleviate the programming burden by incurring overhead in these two domains. We formulate the notions of communicable memory and lazy barriers to help achieve efficient communication and synchronization. These concepts are developed in the context of BSPk, a toolkit library for programming networks of workstations|and other distributed memory architectures in general|based on the Bulk Synchronous Parallel (BSP) model. BSPk emphasizes efficiency in communication by minimizing local memory-to-memory copying, and in barrier synchronization by not forcing a process to wait unless it needs remote data. Both the message passing (MP) and distributed shared memory (DSM) programming styles are supported in BSPk. MP helps processes efficiently exchange short-lived unnamed data values, when the identity of either the sender or receiver is known to the other party. By contrast, DSM supports communication between processes that may be mutually anonymous, so long as they can agree on variable names in which to store shared temporary or long-lived data.

Enforcing precariousness: a comparative analysis of the limitations placed on the legal status of refugees

This thesis focuses on the manner in which the EU, the UK, and Canada respond to and engage with the refugee’s movement from a temporary to a more permanent legal status in the state. It is noted that this transition is increasingly problematized. A trend is noted in response to this among the jurisdictions examined, to exceptionalise refugee status through acts of legal categorisation and separation. These categorisations represent an attempt to re-assert control over refugees who arrived to the state in a spontaneous manner. I argue that this categorisation and fragmentation of refugee status is another means of managing life in the state and ultimately excluding refugees within the state. Refugees therefore experience a contradictory response to their presence. While they are continually reminded of the temporary nature of their legal status in the state, they are still required to demonstrate a willingness to integrate in to the host society. Their behaviour in the state is something that is once again recalled by the decision makers who determine whether they should ultimately be able to access citizenship status. In this thesis, I argue that in order to navigate a route to citizenship, the refugee must respond to the constant re-framing and re-contextualisation of her status in the state of asylum. As the thesis observes, this raises broader questions about the nature of citizenship and belonging

Similar T-cell immune responses induced by group M consensus env immunogens with wild-type or minimum consensus variable regions.

Consensus HIV-1 genes can decrease the genetic distances between candidate immunogens and field virus strains. To ensure the functionality and optimal presentation of immunologic epitopes, we generated two group-M consensus env genes that contain variable regions either from a wild-type B/C recombinant virus isolate (CON6) or minimal consensus elements (CON-S) in the V1, V2, V4, and V5 regions. C57BL/6 and BALB/c mice were primed twice with CON6, CON-S, and subtype control (92UG37_A and HXB2/Bal_B) DNA and boosted with recombinant vaccinia virus (rVV). Mean antibody titers against 92UG37_A, 89.6_B, 96ZM651_C, CON6, and CON-S Env protein were determined. Both CON6 and CON-S induced higher mean antibody titers against several of the proteins, as compared with the subtype controls. However, no significant differences were found in mean antibody titers in animals immunized with CON6 or CON-S. Cellular immune responses were measured by using five complete Env overlapping peptide sets: subtype A (92UG37_A), subtype B (MN_B, 89.6_B and SF162_B), and subtype C (Chn19_C). The intensity of the induced cellular responses was measured by using pooled Env peptides; T-cell epitopes were identified by using matrix peptide pools and individual peptides. No significant differences in T-cell immune-response intensities were noted between CON6 and CON-S immunized BALB/c and C57BL/6 mice. In BALB/c mice, 10 and eight nonoverlapping T-cell epitopes were identified in CON6 and CON-S, whereas eight epitopes were identified in 92UG37_A and HXB2/BAL_B. In C57BL/6 mice, nine and six nonoverlapping T-cell epitopes were identified after immunization with CON6 and CON-S, respectively, whereas only four and three were identified in 92UG37_A and HXB2/BAL_B, respectively. When combined together from both mouse strains, 18 epitopes were identified. The group M artificial consensus env genes, CON6 and CON-S, were equally immunogenic in breadth and intensity for inducing humoral and cellular immune responses.

In situ synthesis of DNA microarray on functionalized cyclic olefin copolymer substrate.

Thermoplastic materials such as cyclic-olefin copolymers (COC) provide a versatile and cost-effective alternative to the traditional glass or silicon substrate for rapid prototyping and industrial scale fabrication of microdevices. To extend the utility of COC as an effective microarray substrate, we developed a new method that enabled for the first time in situ synthesis of DNA oligonucleotide microarrays on the COC substrate. To achieve high-quality DNA synthesis, a SiO(2) thin film array was prepatterned on the inert and hydrophobic COC surface using RF sputtering technique. The subsequent in situ DNA synthesis was confined to the surface of the prepatterned hydrophilic SiO(2) thin film features by precision delivery of the phosphoramidite chemistry using an inkjet DNA synthesizer. The in situ SiO(2)-COC DNA microarray demonstrated superior quality and stability in hybridization assays and thermal cycling reactions. Furthermore, we demonstrate that pools of high-quality mixed-oligos could be cleaved off the SiO(2)-COC microarrays and used directly for construction of DNA origami nanostructures. It is believed that this method will not only enable synthesis of high-quality and low-cost COC DNA microarrays but also provide a basis for further development of integrated microfluidics microarrays for a broad range of bioanalytical and biofabrication applications.

The dopamine metabolite 3-methoxytyramine is a neuromodulator.

Dopamine (3-hydroxytyramine) is a well-known catecholamine neurotransmitter involved in multiple physiological functions including movement control. Here we report that the major extracellular metabolite of dopamine, 3-methoxytyramine (3-MT), can induce behavioral effects in a dopamine-independent manner and these effects are partially mediated by the trace amine associated receptor 1 (TAAR1). Unbiased in vivo screening of putative trace amine receptor ligands for potential effects on the movement control revealed that 3-MT infused in the brain is able to induce a complex set of abnormal involuntary movements in mice acutely depleted of dopamine. In normal mice, the central administration of 3-MT caused a temporary mild hyperactivity with a concomitant set of abnormal movements. Furthermore, 3-MT induced significant ERK and CREB phosphorylation in the mouse striatum, signaling events generally related to PKA-mediated cAMP accumulation. In mice lacking TAAR1, both behavioral and signaling effects of 3-MT were partially attenuated, consistent with the ability of 3-MT to activate TAAR1 receptors and cause cAMP accumulation as well as ERK and CREB phosphorylation in cellular assays. Thus, 3-MT is not just an inactive metabolite of DA, but a novel neuromodulator that in certain situations may be involved in movement control. Further characterization of the physiological functions mediated by 3-MT may advance understanding of the pathophysiology and pharmacology of brain disorders involving abnormal dopaminergic transmission, such as Parkinson's disease, dyskinesia and schizophrenia.

Safety and immunogenicity of a replication-defective adenovirus type 5 HIV vaccine in Ad5-seronegative persons: a randomized clinical trial (HVTN 054).

BACKGROUND: Individuals without prior immunity to a vaccine vector may be more sensitive to reactions following injection, but may also show optimal immune responses to vaccine antigens. To assess safety and maximal tolerated dose of an adenoviral vaccine vector in volunteers without prior immunity, we evaluated a recombinant replication-defective adenovirus type 5 (rAd5) vaccine expressing HIV-1 Gag, Pol, and multiclade Env proteins, VRC-HIVADV014-00-VP, in a randomized, double-blind, dose-escalation, multicenter trial (HVTN study 054) in HIV-1-seronegative participants without detectable neutralizing antibodies (nAb) to the vector. As secondary outcomes, we also assessed T-cell and antibody responses. METHODOLOGY/PRINCIPAL FINDINGS: Volunteers received one dose of vaccine at either 10(10) or 10(11) adenovector particle units, or placebo. T-cell responses were measured against pools of global potential T-cell epitope peptides. HIV-1 binding and neutralizing antibodies were assessed. Systemic reactogenicity was greater at the higher dose, but the vaccine was well tolerated at both doses. Although no HIV infections occurred, commercial diagnostic assays were positive in 87% of vaccinees one year after vaccination. More than 85% of vaccinees developed HIV-1-specific T-cell responses detected by IFN-γ ELISpot and ICS assays at day 28. T-cell responses were: CD8-biased; evenly distributed across the three HIV-1 antigens; not substantially increased at the higher dose; and detected at similar frequencies one year following injection. The vaccine induced binding antibodies against at least one HIV-1 Env antigen in all recipients. CONCLUSIONS/SIGNIFICANCE: This vaccine appeared safe and was highly immunogenic following a single dose in human volunteers without prior nAb against the vector. TRIAL REGISTRATION: ClinicalTrials.gov NCT00119873.