Participation of the nuclear cap binding complex in pre-mRNA 3′ processing

Communication between the 5′ and 3′ ends is a common feature of several aspects of eukaryotic mRNA metabolism. In the nucleus, the pre-mRNA 5′ end is bound by the nuclear cap binding complex (CBC). This RNA–protein complex plays an active role in both splicing and RNA export. We provide evidence for participation of CBC in the processing of the 3′ end of the message. Depletion of CBC from HeLa cell nuclear extract strongly reduced the endonucleolytic cleavage step of the cleavage and polyadenylation process. Cleavage was restored by addition of recombinant CBC. CBC depletion was found to reduce the stability of poly(A) site cleavage complexes formed in nuclear extract. We also provide evidence that the communication between the 5′ and 3′ ends of the pre-mRNA during processing is mediated by the physical association of the CBC/cap complex with 3′ processing factors bound at the poly(A) site. These observations, along with previous data on the function of CBC in splicing, illustrate the key role played by CBC in pre-mRNA recognition and processing. The data provides further support for the hypothesis that pre-mRNAs and mRNAs may exist and be functional in the form of “closed-loops,” due to interactions between factors bound at their 5′ and 3′ ends.

p19Arf induces p53-dependent apoptosis during Abelson virus-mediated pre-B cell transformation

The Ink4a/Arf locus encodes p16Ink4a and p19Arf and is among the most frequently mutated tumor suppressor loci in human cancer. In mice, many of these effects appear to be mediated by interactions between p19Arf and the p53 tumor-suppressor protein. Because Tp53 mutations are a common feature of the multistep pre-B cell transformation process mediated by Abelson murine leukemia virus (Ab-MLV), we examined the possibility that proteins encoded by the Ink4a/Arf locus also play a role in Abelson virus transformation. Analyses of primary transformants revealed that both p16Ink4a and p19Arf are expressed in many of the cells as they emerge from the apoptotic crisis that characterizes the transformation process. Analyses of primary transformants from Ink4a/Arf null mice revealed that these cells bypassed crisis. Because expression of p19Arf but not p16 Ink4a induced apoptosis in Ab-MLV-transformed pre-B cells, p19Arf appears to be responsible for these events. Consistent with the link between p19Arf and p53, Ink4a/Arf expression correlates with or precedes the emergence of cells expressing mutant p53. These data demonstrate that p19Arf is an important part of the cellular defense mounted against transforming signals from the Abl oncoprotein and provide direct evidence that the p19Arf–p53 regulatory loop plays an important role in lymphoma induction.

Immunoglobulin variable region hypermutation in hybrids derived from a pre-B- and a myeloma cell line.

Somatic mutation of the variable (V) regions of immunoglobulin genes occurs in vivo at rates that have been estimated to be between 10(-3) and 10(-4) per bp per generation. To study this process in vitro, the 18.81 pre-B-cell line and hybrids derived by fusing 18.81 to the NSO myeloma fusion partner were transfected with a mu heavy-chain construct containing a nonsense mutation in the V region (Vn) or the constant region (Cn). Mutation was quantitated by reversion analysis using the ELISA spot assay to detect single cells secreting IgM. Fluctuation analysis revealed that V-region mutations spontaneously occurred in 18.81 cells at an average rate of 5.8 x 10(-6) per bp per cell generation and in selected 18.81-NSO hybrids at greatly increased rates of 1.6 x 10(-3) to 5.8 x 10(-4) per bp per generation. The Vn construct also reverted frequently in transgenic mice, indicating that it contained sufficient information to mutate at high rates both in vivo and in vitro. Sequence analysis of reverted genes revealed that reversion was due to point mutations. Since the rates and nature of the mutations that are occurring in these transfected genes are similar to those reported in vivo, it should be possible to use this system to identify the cis-acting sequences and trans-acting factors that are responsible for V-region somatic hypermutation.

Electrochemical synthesis at pre-pilot scale of 1-phenylethanol by cathodic reduction of acetophenone using a solid polymer electrolyte

The pre-pilot scale synthesis of 1-phenylethanol was carried out by the cathodic hydrogenation of acetophenone in a 100 cm2 (geometric area) Polymer Electrolyte Membrane Electrochemical Reactor. The cathode was a Pd/C electrode. Hydrogen oxidation on a gas diffusion electrode was chosen as anodic reaction in order to take advantage of the hydrogen evolved during the reduction. This hydrogen oxidation provides the protons needed for the synthesis. The synthesis performed with only a solid polymer electrolyte, spe, has lower fractional conversion although a higher selectivity than that carried out using a support–electrolyte–solvent together with a spe. However, the difference between these two cases is rather small and since the work-up and purification of the final product are much easier when only a spe is used, this last process was chosen for the pre-pilot electrochemical synthesis of 1-phenylethanol.

Development of a Mechanism and Process to Continuously Produce Spherical, Torrefied Biomass

Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2016-06-17 02:15:25.215

The New Instrument for Pre-Accession Assistance (IPA II): Less Accession, More Assistance?. EIPA Working Paper 2014/W/01

The EU enlargement engine seems to have run out of political steam. Support within the member countries for future enlargement is at all-time low, while some of the candidate countries have also seemed to put the enlargement process on the backburner. However, at least rhetorically, the EU is still committed to the enlargement process and maintains its entire enlargement tool box, such as the Instrument for Pre-Accession (IPA) – one of the most important EU external financial instruments. The new IPA regulation (IPA II), adopted in March 20141, clearly reflects the fact that the enlargement process is on a holding pattern.

Structure as Process: The Regularized Intergovernmentalism of Franco-German Bilateralism, CES Germany & Europe Working Papers, No.02.3, 2002

This article systematically scrutinizes the intergovernmental and administrative aspects of Franco- German relations with the 1963 Elysée Treaty at their core. This treaty, together with its various additions and extensions, has defined the basic processes of bilateral interaction between the French and German states. Recurrent tension in Franco-German relations notwithstanding, many observers and participants have viewed France and Germany to be connected particularly closely since the 1960s. This article explores key elements of what it is that links France and Germany. Thereby it clarifies the concept of regularized intergovernmentalism, suggests viewing this specific set of international practices from a social-structural perspective, and evaluates the effects and limits of such regularized procedures. Its findings suggest that bilateral structures have complemented and undergirded a broadly multilateral post-World War II world and are likely to continue to do.

The EU’s Decision-Making Process Changes in the Constitutive Treaties

Since the beginning of its existence in the form of communities, the European Union’s decision-making process underwent constant evolution. There were continuous adjustments that transformed a pure intergovernmental process into one having rather federal features. Based on the hypothesis that changes have occurred at the decision level in regards to the actors, procedures, influence and ways of taking decisions in order for the new realities, needs and will at the European level to be properly addressed, this paper aims to present the reforms performed through the adoption of new treaties and the modification of the existing ones. The reality is that in order for the European dream and integration to go on and also for further development of the European Union, finally becoming an entity far beyond the founders expectations, decision makers had to constantly and carefully adapt the decision-making process. The purpose of this paper will be achieved by conducting a research based on the qualitative method, analyzing the related researches on this topic and the consolidated versions of the treaties. Thus, we will finally validate our research hypothesis that there was an evolution in what the EU’s decision-making process and decision procedures are concerned.

Reasons withheld and insufficient reasoning as due process violations: two cases before the ECHR

Two very different cases decided by the European Court of Human Rights illustrate how the non-availability of sufficient reasons, for pre-trial judicial decisions in one case, and for a decision in a civil and administrative matter in the other, can lead to due process violations in terms of Articles 5 or 6 of the Convention of Human Rights and Fundamental Freedoms.

La Russie au XVIIe siècle : mémoires inédits sur les règnes de Piere le Grand, Catherne Ire et Pierre II, publiés et précédés d'une introduction /

"Reproduced by Duopage process ... Bell & Howell Company, Cleveland ... Ohio".

Impact of pre-existing sulfate on retention of imported chloride and nitrate in variable charge soil profiles

In variable charge soils, anion retention and accumulation through adsorption at exchange sites is a competitive process. The objectives of this study in the wet tropics of far north Queensland were to investigate (i) whether the pre-existing high sulphate in variable charge soils had any impact on the retention of chloride and nitrate, derived mostly from the applied fertilizer; and (ii) whether chloride competed with nitrate during the adsorption processes. Soil cores up to 12.5 m depth were taken from seven sites, representing four soil types, in the Johnstone River Catchment. Six of these sites had been under sugarcane (Saccharum officinarum-S) cultivation for at least 50 years and one was an undisturbed rainforest. The cores were segmented at 1.0 m depth increments, and subsamples were analysed for nitrate-N, cation (CEC)- and anion-exchange capacities (AEC), pH, exchangeable cations (Ca, Mg, K, Na), soil organic C (SOC), electrical conductivity (EC), sulphate-S, and chloride. Sulphate-S load in 1-12 m depth under cropping ranged from 9.4 to 73.9 t ha(-1) (mean= 40 t ha(-1)) compared with 74.4 t ha(-1) in the rainforest. Chloride load under cropping ranged from 1.5 to 9.6 t ha(-1) (mean= 4.9 t ha(-1)) compared to 0.9 t ha(-1) in the rainforest, and the nitrate-N load from 113 to 2760 kg ha(-1) (mean = 910 kg ha(-1)) under cropping compared to 12 kg ha(-1) in the rainforest. Regardless of the soil type, the total chloride or nitrate-N input in fertilisers was 7.5 t ha(-1), during the last 50 years. Sulphate-S distribution in soil profiles decreased with depth at >2 m, whereas bulges of chloride or nitrate-N were observed at depths >2 m. This suggests that chloride or nitrate adsorption and retention increased with decreasing sulphate dominance. Abrupt decreases in equivalent fraction of sulphate (EFSO4), at depths >2 m, were accompanied by rapid increases in equivalent fraction of chloride (EFCl), followed by nitrate (EFNO3). The stepwise regression for EFCl and EFNO3 indicated that nitrate retention was reduced by the pre-existing sulphate and imported chloride, whereas only sulphate reduced chloride adsorption. The results indicate that chloride and nitrate adsorption and retention occurred, in the order chloride>nitrate, in soils containing large amounts of sulphate under approximately similar total inputs of N- and Cl-fertilisers. (C) 2004 Elsevier B.V. All rights reserved.

Specification and validation of process constraints for flexible workflows

Workflow systems have traditionally focused on the so-called production processes which are characterized by pre-definition, high volume, and repetitiveness. Recently, the deployment of workflow systems in non-traditional domains such as collaborative applications, e-learning and cross-organizational process integration, have put forth new requirements for flexible and dynamic specification. However, this flexibility cannot be offered at the expense of control, a critical requirement of business processes. In this paper, we will present a foundation set of constraints for flexible workflow specification. These constraints are intended to provide an appropriate balance between flexibility and control. The constraint specification framework is based on the concept of pockets of flexibility which allows ad hoc changes and/or building of workflows for highly flexible processes. Basically, our approach is to provide the ability to execute on the basis of a partially specified model, where the full specification of the model is made at runtime, and may be unique to each instance. The verification of dynamically built models is essential. Where as ensuring that the model conforms to specified constraints does not pose great difficulty, ensuring that the constraint set itself does not carry conflicts and redundancy is an interesting and challenging problem. In this paper, we will provide a discussion on both the static and dynamic verification aspects. We will also briefly present Chameleon, a prototype workflow engine that implements these concepts. (c) 2004 Elsevier Ltd. All rights reserved.

Gas and particle dynamics of a contoured shock tube for pre-clinical microparticle drug delivery

We investigate the gas-particle dynamics of a device designed for biological pre-clinical experiments. The device uses transonic/supersonic gas flow to accelerate microparticles such that they penetrate the outer skin layers. By using a shock tube coupled to a correctly expanded nozzle, a quasi-one-dimensional, quasi-steady flow (QSF) is produced to uniformly accelerate the microparticles. The system utilises a microparticle cassette (a diaphragm sealed container) that incorporates a jet mixing mechanism to stir the particles prior to diaphragm rupture. Pressure measurements reveal that a QSF exit period - suitable for uniformly accelerating microparticles - exists between 155 and 220 mus after diaphragm rupture. Immediately preceding the QSF period, a starting process secondary shock was shown to form with its (x,t) trajectory comparing well to theoretical estimates. To characterise the microparticle, flow particle image velocimetry experiments were conducted at the nozzle exit, using particle payloads with varying diameter (2.7-48 mu m), density (600-16,800 kg/m(3)) and mass (0.25-10 mg). The resultant microparticle velocities were temporally uniform. The experiments also show that the starting process does not significantly influence the microparticle nozzle exit velocities. The velocity distribution across the nozzle exit was also uniform for the majority of microparticle types tested. For payload masses typically used in pre-clinical drug and vaccine applications (

Customer information system data pre-processing with feature selection techniques for non-technical losses prediction in an electricity market

Non-technical losses (NTL) identification and prediction are important tasks for many utilities. Data from customer information system (CIS) can be used for NTL analysis. However, in order to accurately and efficiently perform NTL analysis, the original data from CIS need to be pre-processed before any detailed NTL analysis can be carried out. In this paper, we propose a feature selection based method for CIS data pre-processing in order to extract the most relevant information for further analysis such as clustering and classifications. By removing irrelevant and redundant features, feature selection is an essential step in data mining process in finding optimal subset of features to improve the quality of result by giving faster time processing, higher accuracy and simpler results with fewer features. Detailed feature selection analysis is presented in the paper. Both time-domain and load shape data are compared based on the accuracy, consistency and statistical dependencies between features.