Selective Ablation of the Androgen Receptor in Mouse Sertoli Cells Affects Sertoli Cell Maturation, Barrier Formation and Cytoskeletal Development

The observation that mice with a selective ablation of the androgen receptor (AR) in Sertoli cells (SC) (SCARKO mice) display a complete block in meiosis supports the contention that SC play a pivotal role in the control of germ cell development by androgens. To delineate the physiological and molecular mechanism responsible for this control, we compared tubular development in pubertal SCARKO mice and littermate controls. Particular attention was paid to differences in SC maturation, SC barrier formation and cytoskeletal organization and to the molecular mediators potentially involved. Functional analysis of SC barrier development by hypertonic perfusion and lanthanum permeation techniques and immunohistochemical analysis of junction formation showed that SCARKO mice still attempt to produce a barrier separating basal and adluminal compartment but that barrier formation is delayed and defective. Defective barrier formation was accompanied by disturbances in SC nuclear maturation (immature shape, absence of prominent, tripartite nucleoli) and SC polarization (aberrant positioning of SC nuclei and cytoskeletal elements such as vimentin). Quantitative RT-PCR was used to study the transcript levels of genes potentially related to the described phenomena between day 8 and 35. Differences in the expression of SC genes known to play a role in junction formation could be shown from day 8 for Cldn11, from day 15 for Cldn3 and Espn, from day 20 for Cdh2 and Jam3 and from day 35 for ZO-1. Marked differences were also noted in the transcript levels of several genes that are also related to cell adhesion and cytoskeletal dynamics but that have not yet been studied in SC (Actn3, Ank3, Anxa9, Scin, Emb, Mpzl2). It is concluded that absence of a functional AR in SC impedes the remodeling of testicular tubules expected at the onset of spermatogenesis and interferes with the creation of the specific environment needed for germ cell development.

The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

ENERGY GENERATION EXPANSION PLANNING MODEL CONSIDERING EMISSIONS CONSTRAINTS

The generation expansion planning (GEP) problem consists in determining the type of technology, size, location and time at which new generation units must be integrated to the system, over a given planning horizon, to satisfy the forecasted energy demand. Over the past few years, due to an increasing awareness of environmental issues, different approaches to solve the GEP problem have included some sort of environmental policy, typically based on emission constraints. This paper presents a linear model in a dynamic version to solve the GEP problem. The main difference between the proposed model and most of the works presented in the specialized literature is the way the environmental policy is envisaged. Such policy includes: i) the taxation of CO(2) emissions, ii) an annual Emissions Reduction Rate (ERR) in the overall system, and iii) the gradual retirement of old inefficient generation plants. The proposed model is applied in an 11-region to design the most cost-effective and sustainable 10-technology US energy portfolio for the next 20 years.

An implementation of modified scatter search algorithm to transmission expansion planning

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparative studies on non-convex optimization methods for transmission network expansion planning

We have investigated and extensively tested three families of non-convex optimization approaches for solving the transmission network expansion planning problem: simulated annealing (SA), genetic algorithms (GA), and tabu search algorithms (TS). The paper compares the main features of the three approaches and presents an integrated view of these methodologies. A hybrid approach is then proposed which presents performances which are far better than the ones obtained with any of these approaches individually. Results obtained in tests performed with large scale real-life networks are summarized.

The δ expansion and the principle of minimal sensitivity

The δ-expansion is a nonperturbative approach for field theoretic models which combines the techniques of perturbation theory and the variational principle. Different ways of implementing the principle of minimal sensitivity to the δ-expansion produce in general different results for observables. For illustration we use the Nambu-Jona-Lasinio model for chiral symmetry restoration at finite density and compare results with those obtained with the Hartree-Fock approximation.

Renal effects of angiotensin II receptor subtype 1 and 2-selective ligands injected into the paraventricular nucleus of conscious rats

We determined the effects of losartan and CGP42112A (selective ligands of the AT1 and AT2 angiotensin receptors, respectively) and salarasin (a relatively nonselective angiotensin receptor antagonist) on urinary volume and urinary sodium and potassium excretion induced by administration of angiotensin II (ANG II) into the paraventricular nucleus (PVN) of conscious rats. Both the AT1 and AT2 ligands and salarasin administered in the presence of ANG II elicited a concentration-dependent inhibition of urine excretion, but losartan inhibited only 75% of this response. The IC50 for salarasin, CGP42112A, and losartan was 0.01, 0.05, and 6 nM, respectively. Previous treatment with saralasin, CGP42112A and losartan competitively antagonized the natriuretic responses to PVN administration of ANG II, and the IC50 values were 0.09, 0.48, and 10 nM, respectively. The maximum response to losartan was 65% of that obtained with saralasin. Pretreatment with saralasin, losartan, and CGP42112A injected into the PVN caused shifts to the right of the concentration-response curves, but the losartan concentrations were disproportionately greater compared with salarasin or CGP42112A. The IC50 values were 0.06, 0.5, and 7.0 for salarasin, CGP42112A, and losartan, respectively. These results suggest that both AT1 and AT2 receptor subtypes in the PVN are involved in ANG II-related urine, sodium, and potassium excretion, and that the inhibitory responses to AT2 blockade are predominant. Copyright (C) 1999 Elsevier Science B.V.

Structure of thrombin complexed with selective non-electrophilic inhibitors having cyclohexyl moieties at P1

The crystal structures of five new non-electrophilic β-strand-templated thrombin active-site inhibitors have been determined bound to the enzyme. Four co-crystallize with hirugen and inhibitor isomorphously to produce thrombin-hirugen crystals (monoclinic, space group C2), while one co-crystallizes in the hexagonal system, space group P65. A 1,4-substituted cyclohexyl moiety is conserved at the P1 position of all the inhibitors, along with a fused hetero-bicyclic five- and six-membered ring that occupies the P2 site. Amino, amidino and aminoimidazole groups are attached to the cyclohexyl ring for recognition at the S1 specificity site, while benzylsulfonyl and diphenyl groups enhance the binding at the S3 subsite. The cyclohexyl groups at the P1 positions of three of the inhibitors appear to be in the energetically favored chair conformation, while the imidazole-substituted cyclohexyl rings are in a boat conformation. Somewhat unexpectedly, the two cyclohexyl-aminoimidazole groups bind differently in the specificity site; the unique binding of one is heretofore unreported. The other inhibitors generally mimic arginyl binding at S1. This group of inhibitors combines the nonelectrophilicity and selectivity of DAPA-like compounds and the more optimal binding features of the S1-S3 sites of thrombin for peptidic molecules, which results in highly potent (binding constants 12 nM-16 pM, one being 1.1 μM) and selective (ranging from 140 to 20 000 times more selective compared with trypsin) inhibitors of thrombin. The binding modes of these novel inhibitors are correlated with their binding constants, as is their selectivity, in order to provide further insight for the design of therapeutic antithrombotic agents that inhibit thrombin directly at the active site.

Optimized delta expansion for relativistic nuclear models: Renormalization of vacuum fluctuations

We use the optimized linear δ expansion and functional methods to study vacuum contributions in nuclear matter up to the lowest non-trivial order which includes exchange terms. We show that well known results (MFT, RHA and HF) can be easily reproduced when appropriate limits are taken. Neglecting vacuum contributions we explicitly show that the δ expansion goes beyond the traditional loop approximation previously used to study two loop vacuum contributions in nuclear matter. We then evaluate and renormalize vacuum exchange contributions showing that they are numerically very large, as predicted by the ordinary loop approximation.

Free expansion of attractive and repulsive Bose-Einstein condensed vortex states

A numerical study of the time-dependent Gross-Pitaevskii equation for an axially symmetric trap to obtain insight into the free expansion of vortex states of BEC is presented. As such, the ratio of vortex-core radius to radia rms radius xc/xrms(<1) is found to play an interesting role in the free expansion of condensed vortex states. the larger this ratio, the more prominent is the vortex core and the easier is the possibility of experimental detection of vortex states.

A constructive heuristic algorithm to Short Term Transmission Network Expansion Planning

In this paper a method for solving the Short Term Transmission Network Expansion Planning (STTNEP) problem is presented. The STTNEP is a very complex mixed integer nonlinear programming problem that presents a combinatorial explosion in the search space. In this work we present a constructive heuristic algorithm to find a solution of the STTNEP of excellent quality. In each step of the algorithm a sensitivity index is used to add a circuit (transmission line or transformer) to the system. This sensitivity index is obtained solving the STTNEP problem considering as a continuous variable the number of circuits to be added (relaxed problem). The relaxed problem is a large and complex nonlinear programming and was solved through an interior points method that uses a combination of the multiple predictor corrector and multiple centrality corrections methods, both belonging to the family of higher order interior points method (HOIPM). Tests were carried out using a modified Carver system and the results presented show the good performance of both the constructive heuristic algorithm to solve the STTNEP problem and the HOIPM used in each step.

A branch-and-bound algorithm for the multi-stage transmission expansion planning

This work presents a branch-and-bound algorithm to solve the multi-stage transmission expansion planning problem. The well known transportation model is employed, nevertheless the algorithm can be extended to hybrid models or to more complex ones such as the DC model. Tests with a realistic power system were carried out in order to show the performance of the algorithm for the expansion plan executed for different time frames. © 2005 IEEE.

Transmission network expansion planning in full open market considering security constraints

This paper presents a mathematical model and a methodology to solve the transmission network expansion planning problem with security constraints in full competitive market, assuming that all generation programming plans present in the system operation are known. The methodology let us find an optimal transmission network expansion plan that allows the power system to operate adequately in each one of the generation programming plans specified in the full competitive market case, including a single contingency situation with generation rescheduling using the security (n-1) criterion. In this context, the centralized expansion planning with security constraints and the expansion planning in full competitive market are subsets of the proposal presented in this paper. The model provides a solution using a genetic algorithm designed to efficiently solve the reliable expansion planning in full competitive market. The results obtained for several known systems from the literature show the excellent performance of the proposed methodology.

Periodontal effects of rapid maxillary expansion with tooth-tissue-borne and tooth-borne expanders: A computed tomography evaluation

Introduction: The force delivered during rapid maxillary expansion (RME) produces areas of compression on the periodontal ligament of the supporting teeth. The resulting alveolar bone resorption can lead to unwanted tooth movement in the same direction. The purpose of this study was to evaluate periodontal changes by means of computed tomography after RME with tooth-tissue-borne and tooth-borne expanders. Methods: The sample comprised 8 girls, 11 to 14 years old, with Class I or II malocclusions with unilateral or bilateral posterior crossbites Four girls were treated with tooth-tissue-borne Haas-type expanders, and 4 were treated with tooth-borne Hyrax expanders. The appliances were activated up to the full 7-mm capacity of the expansion screw. Spiral CT scans were taken before expansion and after the 3-month retention period when the expander was removed. One-millimeter thick axial sections were exposed parallel to the palatal plane, comprising the dentoalveolar area and the base of the maxilla up to the inferior third of the nasal cavity. Multiplanar reconstruction was used to measure buccal and lingual bone plate thickness and buccal alveolar bone crest level by means of the computerized method. Results and Conclusions: RME reduced the buccal bone plate thickness of supporting teeth 0.6 to 0.9 mm and increased the lingual bone plate thickness 0.8 to 1.3 mm. The increase in lingual bone plate thickness of the maxillary posterior teeth was greater in the tooth-borne expansion group than in the tooth-tissue-borne group. RME induced bone dehiscences on the anchorage teeth's buccal aspect (7.1 ± 4.6 mm at the first premolars and 3.8 ± 4.4 mm at the mesiobuccal area of the first molars), especially in subjects with thinner buccal bone plates. The tooth-borne expander produced greater reduction of first premolar buccal alveolar bone crest level than did the tooth-tissue-borne expander. © 2006 American Association of Orthodontists.