The 2000 Ogura Lecture: Olfactory neural cells: An untapped diagnostic and therapeutic resource

Objective. This is an over-view of the cellular biology of upper nasal mucosal cells that have special characteristics that enable them to be used to diagnose and study congenital neurological diseases and to aid neural repair. Study Design: After mapping the distribution of neural cells in the upper nose, the authors' investigations moved to the use of olfactory neurones to diagnose neurological diseases of development, especially schizophrenia. Olfactory-ensheating glial cells (OEGs) from the cranial cavity promote axonal penetration of the central nervous system and aid spinal cord repair in rodents. The authors sought to isolate these cells from the more accessible upper nasal cavity in rats and in humans and prove they could likewise promote neural regeneration, making these cells suitable for human spinal repair investigations. Methods: The schizophrenia-diagnosis aspect of the study entailed the biopsy of the olfactory areas of 10 schizophrenic patients and 10 control subjects. The tissue samples were sliced and grown in culture medium. The ease of cell attachment to fibronectin (artificial epithelial basement membrane), as well as the mitotic and apoptotic indices, was studied in the presence and absence of dopamine in those cell cultures. The neural repair part of the study entailed a harvesting and insertion of first rat olfactory lamina propria rich in OEGs between cut ends of the spinal cords and then later the microinjection of an OEG-rich suspension into rat spinal cords previously transected by open laminectomy. Further studies were done in which OEG insertion was performed up to 1 month after rat cord transection and also in monkeys. Results: Schizophrenic patients' olfactory tissues do not easily attach to basement membrane compared with control subjects, adding evidence to the theory that cell wall anomalies are part of the schizophrenic lesion of neurones. Schizophrenic patient cell cultures had higher mitotic and apoptotic indices compared with control subjects. The addition of dopamine altered these indices enough to allow accurate differentiation of schizophrenics from control patients, leading to, possibly for the first time, an early objective diagnosis of schizophrenia and possible assessment of preventive strategies. OEGs from the nose were shown to be as effective as those from the olfactory bulb in promoting axonal growth across transected spinal cords even when added I month after injury in the rat. These otherwise paraplegic rats grew motor and proprioceptive and fine touch fibers with corresponding behavioral improvement. Conclusions. The tissues of the olfactory mucosa are readily available to the otolaryngologist. Being surface cells, they must regenerate (called neurogenesis). Biopsy of this area and amplification of cells in culture gives the scientist a window to the developing brain, including early diagnosis of schizophrenia. The Holy Grail of neurological disease is the cure of traumatic paraplegia and OEGs from the nose promote that repair. The otolaryngologist may become the necessary partner of the neurophysiologist and spinal surgeon to take the laboratory potential of paraplegic cure into the day-to-day realm of clinical reality.

Carbamazepine augmentation for schizophrenia: How good is the evidence?

Background: Augmentation strategies in schizophrenia treatment remain an important issue because despite the introduction of several new antipsychotics, many patients remain treatment resistant. The aim of this study was to undertake a systematic review and meta-analysis of the safety and efficacy of one frequently used adjunctive compound: carbamazepine. Data sources and study selection: Randomized controlled trials comparing carbamazopine (as a sole or as an adjunctive compound) with placebo or no intervention in participants with schizophrenia or schizoaffective disorder were searched for by accessing 7 electronic databases, cross-referencing publications cited in pertinent studies, and contacting drug companies that manufacture carbamazepine. Method: The identified studies were independently inspected and their quality assessed by 2 reviewers, Because the study results were generally incompletely reported, original patient data were requested from the authors; data were received for 8 of the 10 randomized controlled trials included in the present analysis, allowing for a reanalysis of the primary data. Dichotomous variables were analyzed using the Mantel-Haenszel odds ratio and continuous data were analyzed using standardized mean differences, both specified with 95% confidence intervals. Results: Ten studies (total N = 283 subjects) were included. Carbamazepine was not effective in preventing relapse in the only randomized controlled trial that compared carbamazepine monotherapy with placebo. Carbamazepine tended to be less effective than perphenazine in the only trial comparing carbamazepine with an antipsychotic. Although there was a trend indicating a benefit from carbamazepine as an adjunct to antipsychotics, this trend did not reach statistical significance. Conclusion: At present, this augmentation strategy cannot be recommended for routine use. The most promising targets for future trials are patients with excitement, aggression, and schizoaffective disorder bipolar type.

Competition and resource availability in an annual plant community dominated by an invasive species, Carrichtera annua (L. Aschers.), in South Australia

The last decade has seen spirited debates about how resource availability affect the intensity of competition. This paper examines the effect that a dominant introduced species, Carrichtera annua, has upon the winter annual community in the arid chenopod shrublands of South Australia. Manipulative field experiments were conducted to assess plant community response to changing below-ground resource levels and to the manipulation of the density of C. annua. Changes in the density of C. annua had little effect on the abundance of all other species in the guild. Nutrient addition produced an increase in the biomass of the most abundant native species, Crassula colorata. An analysis of the root distribution of the main species suggested that the areas of soil resource capture of C. annua and C. colorata are largely segregated. Our results suggest that intraspecific competition may be stronger than interspecific competition, controlling the species responses to increased resource availability. The results are consistent with a two-phase resource dynamics systems, with pulses of high resource availability triggering growth, followed by pulses of stress. Smaller plants were nutrient limited under natural field conditions, suggesting that stress experienced during long interpulse phases may override competitive effects after short pulse phases. The observed differences in root system structure will determine when plants of a different species are experiencing a pulse or an interpulse phase. We suggest that the limitations to plant recruitment and growth are the product of a complex interplay between the length and intensity of the pulse of resource availability, the duration and severity of the interpulse periods, and biological characters of the species.

The blood volumes of the primary and secondary circulatory system in the Atlantic cod Gadus morhua L., using plasma bound Evans Blue and compartmental analysis

The volume of the primary (PCS) and secondary (SCS) circulatory system in the Atlantic cod Gadus morhua was determined using a modified dye dilution technique. Cod (N=10) were chronically cannulated in the second afferent branchial artery with PE-50 tubing. Evans Blue dye was bound to harvested fish plasma at a concentration of 1 mg dye ml(-1) plasma, and injected at a concentration of 1 mg kg(-1) body mass. Serial sampling from the cannula produced a dye dilution curve, which could be described by a double exponential decay equation. Curve analysis enabled the calculation of the primary circulatory and total distribution volume. The difference between these volumes is assumed to be the volume of the SCS. From the dilution curve, it was also possible to calculate flow rates between and within the systems. The results of these experiments suggest a plasma volume in the PCS of 3.42+/-0.89 ml 100 g(-1) body mass, and in the SCS of 1.68+/-0.35 ml 100 g(-1) body mass (mean +/- S.D.) or approximately 50% that of the PCS. Flow rates to the SCS were calculated as 2.7% of the resting cardiac output. There was an allometric relationship between body mass and blood volumes. Increasing condition factor showed a tendency towards smaller blood volumes of the PCS, expressed as percentage body mass, but this was not evident for the volume of the SCS.

Synthesis, stability, antiviral activity, and protease-bound structures of substrate-mimicking constrained macrocyclic inhibitors of HIV-1 protease

Three new peptidomimetics (1-3) have been developed with highly stable and conformationally constrained macrocyclic components that replace tripeptide segments of protease substrates. Each compound inhibits both HIV-1 protease and viral replication (HIV-I, HIV-2) at nanomolar concentrations without cytotoxicity to uninfected cells below 10 mu M. Their activities against HIV-1 protease (K-i 1.7 nM (1), 0.6 nM (2), 0.3 nM (3)) are 1-2 orders of magnitude greater than their antiviral potencies against HIV-1-infected primary peripheral blood mononuclear cells (IC50 45 nM (1), 56 nM (2), 95 nM (3)) or HIV-1-infected MT2 cells (IC50 90 nM (1), 60 nM (2)), suggesting suboptimal cellular uptake. However their antiviral potencies are similar to those of indinavir and amprenavir under identical conditions. There were significant differences in their capacities to inhibit the replication of HIV-1 and HIV-2 in infected MT2 cells, 1 being ineffective against HIV-2 while 2 was equally effective against both virus types. Evidence is presented that 1 and 2 inhibit cleavage of the HIV-1 structural protein precursor Pr55(gag) to p24 in virions derived from chronically infected cells, consistent with inhibition of the viral protease in cells. Crystal structures refined to 1.75 Angstrom (1) and 1.85 Angstrom (2) for two of the macrocyclic inhibitors bound to HIV-1 protease establish structural mimicry of the tripeptides that the cycles were designed to imitate. Structural comparisons between protease-bound macrocyclic inhibitors, VX478 (amprenavir), and L-735,524 (indinavir) show that their common acyclic components share the same space in the active site of the enzyme and make identical interactions with enzyme residues. This substrate-mimicking minimalist approach to drug design could have benefits in the context of viral resistance, since mutations which induce inhibitor resistance may also be those which prevent substrate processing.

Low input tillage/cropping systems for limited resource areas

Agriculture in limited resource areas is characterized by small farms which an generally too small to adequately support the needs of an average farm family. The farming operation can be described as a low input cropping system with the main energy source being manual labor, draught animals and in some areas hand tractors. These farming systems are the most important contributor to the national economy of many developing countries. The role of tillage is similar in dryland agricultural systems in both the high input (HICS) and low input cropping systems (LICS), however, wet cultivation or puddling is unique to lowland rice-based systems in low input cropping systems. Evidence suggest that tillage may result in marginal increases in crop yield in the short term, however, in the longer term it may be neutral or give rise to yield decreases associated with soil structural degradation. On marginal soils, tillage may be required to prepare suitable seedbeds or to release adequate Nitrogen through mineralization, but in the longer term, however, tillage reduces soil organic matter content, increases soil erodibility and the emission of greenhouse gases. Tillage in low input cropping systems involves a very large proportion of the population and any changes: in current practices such as increased mechanization will have a large social impact such as increased unemployment and increasing feminization of poverty, as mechanization may actually reduce jobs for women. Rapid mechanization is likely to result in failures, but slower change, accompanied by measures to provide alternative rural employment, might be beneficial. Agriculture in limited resource areas must produce the food and fiber needs of their community, and its future depends on the development of sustainable tillage/cropping systems that are suitable for the soil and climatic conditions. These should be based on sound biophysical principles and meet the needs of and he acceptable to the farming communities. Some of the principle requirements for a sustainable system includes the maintenance of soil health, an increase in the rain water use efficiency of the system, increased use of fertilizer and the prevention of erosion. The maintenance of crop residues on the surface is paramount for meeting these requirements, and the competing use of crop residues must be met from other sources. These requirements can be met within a zonal tillage system combined with suitable agroforestry, which will reduce the need for crop residues. It is, however, essential that farmers participate in the development of any new technologies to ensure adoption of the new system. (C) 2001 Elsevier Science B.V. All rights reserved.

Calculation of bound and resonance states of HO2 for nonzero total angular momentum

Bound and resonance states of HO2 have been calculated quantum mechanically by the Lanczos homogeneous filter diagonalization method [Zhang and Smith, Phys. Chem. Chem. Phys. 3, 2282 (2001); J. Chem. Phys. 115, 5751 (2001)] for nonzero total angular momentum J = 1,2,3. For lower bound states, agreement between the results in this paper and previous work is quite satisfactory; while for high lying bound states and resonances these are the first reported results. A helicity quantum number V assignment (within the helicity conserving approximation) is performed and the results indicate that for lower bound states it is possible to assign the V quantum numbers unambiguously, but for resonances it is impossible to assign the V helicity quantum numbers due to strong mixing. In fact, for the high-lying bound states, the mixing has already appeared. These results indicate that the helicity conserving approximation is not good for the resonance state calculations and exact quantum calculations are needed to accurately describe the reaction dynamics for HO2 system. Analysis of the resonance widths shows that most of the resonances are overlapping and the interferences between them lead to large fluctuations from one resonance to another. In accord with the conclusions from earlier J = 0 calculations, this indicates that the dissociation of HO2 is essentially irregular. (C) 2003 American Institute of Physics.

Budgeting and resource allocation in universities: a public choice approach

The calls for colleges and universities to improve their productivity are coming thick and fast in Brazil. Many studies are suggesting evaluation systems and external criteria to control the quality of teaching and research in universities. Since universities and colleges are not profit-oriented organizations (considering only the legitimate and serious research and teaching organizations, of course), the traditional microeconomics and administrative variables used to measure efficiency do not have any direct function. An alternative would be to create an "as if" market control system to evaluate performance in universities and colleges. Internal budget and resources allocation mechanism can be used as incentive instruments to improve quality and productivity. It will be the main issue of this article.

COGNITIVE LEGITIMACY, RESOURCE ACCESS, AND ORGANIZATIONAL OUTCOMES

Previous research has demonstrated the importance of developing legitimacy initiatives in order to create new business opportunities, satisfy shareholders, and obtain access to resources. Within this framework, cognitive legitimacy plays a key role. Through a case study of six Spanish public universities, the authors measure the relationship between cognitive legitimacy, access to resources, and organizational results. The results support the assertion that organizations with more cognitive legitimacy have greater access to resources and improved their results. This study contributes with muchneeded empirical research on cognitive legitimacy and demonstrates its usefulness as an explanative factor of organizational success.

Enterprise Resource Planning governamental: a percepção dos servidores atuantes no Projeto Ciclo do Ministério da Justiça quanto à implementação

Indubitavelmente, a implementação de sistemas de gestão integrada é fator consolidado em empresas privadas; no entanto, em empresas públicas é relativamente recente e inovadora. Em 2009, o Ministério da Justiça (MJ) foi um dos pioneiros ao firmar parceria com a Universidade Federal do Rio Grande do Norte (UFRN) para a implantação de sistemas de gestão integrada. Com o decorrer dos processos de implementação surge a necessidade de identificar se o acordo surtiu os efeitos a que se destinou, bem como é pertinente a análise da implementação de um Enterprise Resource Planning (ERP) governamental em uma empresa pública, haja vista que existe uma tendência de que se repita em outras instituições governamentais. Assim, o principal objetivo deste artigo é identificar a percepção dos usuários quanto ao processo de implementação de sistemas integrados de gestão vinculados ao Projeto Ciclo, no âmbito da Secretaria Executiva do MJ, destacando suas principais dificuldades e benefícios. A fim de atingir o objetivo da pesquisa foi realizada uma pesquisa quali-quantitativa, cujo procedimento técnico foi o estudo de caso. Verificou-se que os usuários do sistema reconhecem sua importância como apoio à tomada de decisão, que estão cientes do papel que desempenham no processo de implementação e que a tecnologia da informação (TI) é fundamental para se obter melhoria nos processos executados. Ademais, percebe-se os avanços que um ERP governamental pode proporcionar a empresas públicas, destacando-se o planejamento e a confiabilidade das informações.

A checkpointing-enabled and resource-aware Java Virtual Machine for efficient and robust e-Science applications in grid environments

Object-oriented programming languages presently are the dominant paradigm of application development (e. g., Java,. NET). Lately, increasingly more Java applications have long (or very long) execution times and manipulate large amounts of data/information, gaining relevance in fields related with e-Science (with Grid and Cloud computing). Significant examples include Chemistry, Computational Biology and Bio-informatics, with many available Java-based APIs (e. g., Neobio). Often, when the execution of such an application is terminated abruptly because of a failure (regardless of the cause being a hardware of software fault, lack of available resources, etc.), all of its work already performed is simply lost, and when the application is later re-initiated, it has to restart all its work from scratch, wasting resources and time, while also being prone to another failure and may delay its completion with no deadline guarantees. Our proposed solution to address these issues is through incorporating mechanisms for checkpointing and migration in a JVM. These make applications more robust and flexible by being able to move to other nodes, without any intervention from the programmer. This article provides a solution to Java applications with long execution times, by extending a JVM (Jikes research virtual machine) with such mechanisms. Copyright (C) 2011 John Wiley & Sons, Ltd.

Energy resource scheduling in a real distribution network managed by several virtual power players

Smart Grids (SGs) appeared as the new paradigm for power system management and operation, being designed to integrate large amounts of distributed energy resources. This new paradigm requires a more efficient Energy Resource Management (ERM) and, simultaneously, makes this a more complex problem, due to the intensive use of distributed energy resources (DER), such as distributed generation, active consumers with demand response contracts, and storage units. This paper presents a methodology to address the energy resource scheduling, considering an intensive use of distributed generation and demand response contracts. A case study of a 30 kV real distribution network, including a substation with 6 feeders and 937 buses, is used to demonstrate the effectiveness of the proposed methodology. This network is managed by six virtual power players (VPP) with capability to manage the DER and the distribution network.