Laboratory Testing of SHRP SPS-2 P.C.C. Mixes, MLR-94-5, 1995

This research evaluated the concrete strength of two mixes which were used in the Polk County project NHS-500-1(3)--10-77 and were developed to meet a contract requirement of 900 psi third-point 28-day flexural strength. Two concrete mixes, the Proposed Mix and the Enhanced Mix, were tested for strength. Based on the experimental results, it was found that the addition of 50 lb of cementitious materials did not significantly increase concrete strength. The requirement of 900 psi 28-day third-point flexural strength (MOR-TPL) was not achieved by this amount of addition of cementitious materials.

An Evaluation of the Troxler 3241-B Nuclear Asphalt Gauge, MLR-85-11, 1986

The Troxler 3241-B Asphalt Content Gauge is intended for rapidly determining the bitumen content of bituminous paving mixtures. A 300 Millicurie Americuium 241: Beryllium source emitts neutrons which are affected by the hydrogen in the mix. The affected neutrons are detected by Helium 3 detectors, counted and computed into a percentage bitumen of the asphalt mix. The current methods of determining the bitumen content of bituminous paving mixtures requires the use of potentially hazardous chemicals and several hours of testing time. When extracted aggregates are not needed, determination of the bitumen content of a paving mixture by the nuclear method may be easier, quicker and potentially safer. The objective of the project is to study the accuracy of the Troxler 3241-B Nuclear Asphalt Content Gauge in measuring the asphalt cement (AC) content of asphalt concrete mixtures produced with different asphalt cements and different aggregates.

Targeting receptor activator of nuclear factor-kappa B as a new therapy for bone metastasis in non-small cell lung cancer.

PURPOSE OF REVIEW: The review aims at comprehensively discussing our current knowledge on bone metastases incidence in non-small cell lung cancer (NSCLC), their related complications as well as clinical impact in patients suffering from advanced disease. RECENT FINDINGS: After evoking the use of zoledronic acid as the established standard of care until recently, the new class of drugs available to prevent skeletal related events and targeting receptor activator of nuclear factor-kappa B (RANK) will be emphasized, reporting on denosumab clinical trials, a RANK-ligand (RANKL) targeting monoclonal antibody. Biological hypothesis regarding their mechanisms of action as well a potential direct impact on tumor cells are described according to the most recent laboratory as well as hypothesis-generating clinical data. SUMMARY: Targeting the RANK pathway is an efficient way to prevent complications of bone metastases in NSCLC. Interesting additional direct effects on tumor biology and evolution are being analyzed and prospectively assessed in clinical trials.

The Great Museum of Egypt

Nou museu devant de les piràmides de Giza (El Cairo).Lloc extraordinari i extraordinàriament difícil.Incorpora protecció/ aprofitament del vent del desert, tempestes de sorra i aigua de pluja

Methadone maintenance treatment in the Swiss Canton of Vaud: demographic and clinical data on 1,782 ambulatory patients.

Using data from the Public Health Service, we studied the demographic and clinical characteristics of 1,782 patients enrolled in methadone maintenance treatment (MMT) during 2001 in the Swiss Canton of Vaud, comparing our findings with the results of a previous study from 1976 to 1986. In 2001, most patients (76.9%) were treated in general practice. Mortality is low in this MMT population (1%/year). While patient age and sex profiles were similar to those found in the earlier study, we did observe a substantial increase in the number of patients and the number of practitioners treating MMT patients, probably reflecting the low-threshold governmental policies and the creation of specialized centers. In conclusion, easier access to MMT enhances the number of patients, but new concerns about the quality of management emerge: benzodiazepine as a concomitant prescription; low rates of screening for hepatitis B, C and HIV, and social and psychiatric preoccupations.

Neurobiology of addiction: the role of transcription factors CREB and C/EBP as well as that of their coactivators

Résumé Le présent travail de thèse a fait face au défi de lier les changements transcriptionnels dans les neurones du système nerveux central au développement de l'addiction aux drogues. I1 est connu que l'apprentissage induit des modifications au niveau de la structure du cerveau, principalement en changeant la manière dont les neurones sont interconnectés par des synapses. De plus en plus d'évidences soutiennent un scénario selon lequel l'activité neuronale déclenche des cascades de signalisation intracellulaire qui ciblent des facteurs de transcription. Ces derniers peuvent activer la transcription de gènes spécifiques qui codent pour des protéines nécessaires au renforcement des synapses mémorisant ainsi la nouvelle information. Puisque l'addiction peut être considérée comme une forme aberrante d'apprentissage, et que les modifications synaptiques sont connues pour être impliquées dans le processus d'addiction, nous essayons de décrire des mécanismes transcriptionels étant à la base des changements synaptiques induits par les drogues. Comme modèle nous utilisons des cultures primaires des neurones de striatum, d'hippocampe et de cortex de souris ainsi que des tranches de cerveau de rat. Une des caractéristiques communes de quasiment toutes les substances addictives est de pouvoir activer le système mésolimbique dopaminergique provoquant la libération de dopamine sur les neurones du striatum (du noyau accumbens). Dans ce travail de thèse nous démontrons que dans des cultures du striatum, la dopamine induit le facteur de transcription C/EBPβ qui, à son tour, provoque l'expression du gène codant pour la substance P. Ce mécanisme pourrait potentiellement contribuer à la tolérance envers les drogues puisqu'il fait partie d'une rétroaction (feed-back) sur les cellules produisant la dopamine. Etant donné que ces résultats montrent l'importance de C/EBPβ dans la psychopathologie de l'addiction, nous avons également décidé d'étudier les mécanismes fondamentaux de l'activation de la transcription par C/EBPβ. Nos expériences démontrent que trois isoformes activatrices de la famille C/EBP recrutent le coactivateur CBP et provoquent en même temps sa phosphorylation. Enfin, nous montrons que les coactivateurs nommés TORC, nouvellement découverts et clonés, sont capables de détecter la coïncidence d'un signal cAMP et d'une entrée de calcium dans des neurones. Par conséquent les TORCs pourraient contribuer à détecter la coïncidence d'un signal glutamate et d'un signal dopamine dans les neurones de striatum, ce qui pourrait être important pour associer les effets hédonistes de la drogue à l'information contextuelle (par exemple à l'environnement où la drogue a été consommée). Nous sommes les premiers à observer que les TORCs sont nécessaires pour la potentiation à long terme dans l'hippocampe. Summary The present thesis work faced the challenge to link the development of drug addiction to transcriptional changes in the neurons of the central nervous system. Experience and learning are known to induce structural modifications in the brain, and these changes are thought to occur mainly in the way neurons are interconnected by synapses. More and more evidences point to a scenario in which neuronal activity would activate signalization cascades that impinge on transcription factors, which, in turn, would activate genes necessary for the reinforcement of synapses coding for new informations. Given that drug addiction can be considered as an aberrant form of learning and is thought to involve synaptic modifications, we try to elucidate some of the transcriptional mechanisms that could underlie drug-induced synaptic changes. As a model system, we use primary cultures of striatal, cortical and hippocampal neurons dissected from mouse embryos as well as brain slices from rats. One of the common features of virtually all drugs of abuse is to activate the mesocorticolimbic dopaminergic system that results in the release of dopamine onto the neurons of the striatum (nucleus accumbens). In this thesis work we show that in striatal cultures, dopamine induces the transcription factor C/EBPβ that in turn drives the expression of the gene coding for substance P. This mechanism is likely to be important for the drug-induced tolerance in the brain since it might be a part of a feedback acting on dopaminergic neurons. Given the suspected importance of C/EBPβ in drug addiction, we also try to elucidate some aspects of the basic mechanisms by which the C/EBP family activates transcription. We show that three activating members of the C/EBP family recruit the coactivator CBP and trigger its phosphorylation. Finally, we demonstrate that the newly discovered and cloned transcriptional coactivators, named TORCs (transducers of regulated CREB activity) are able to detect the coincidence of a calcium and a cAMP signal in the central nervous system. This way, TORCs could contribute to the detection of a coincidence between a glutamate and a dopamine signal in striatal neurons - a process that is suggested to be important for an association between the rewarding effect of a drug and contextual information (such as the environment where the drug had been taken). We demonstrate that TORCs are required for hippocampal LTP.

Evaluation of substrates on the emergence of "araticum-de-terra-fria" (Annona emarginata (Schltdl.) H. Rainer) Seedlings

Choosing a substrate is the determinant factor for the seedling producer; thus, the aim of this study was to evaluate the effect of different types of substrates on the emergence of "araticum-de-terra-fria" (Annona emarginata (Schltdl.) H. Rainer) seedlings. The experiment was carried out in a greenhouse and the experimental design was in randomized blocks, with three treatments and five replicates of 72 seeds per plot. The treatments consisted of the following substrates: coconut fiber, vermiculite and Plantmax® Citrus. The number of emerged seedlings was weekly counted for 105 days. Data regarding seedling height were obtained, and the emergence velocity index and mean time, besides total emergence percentage and that over time were calculated. Results from total mean emergence percentage, seedling height, emergence velocity index (EVI), and mean emergence time (MET) were subjected to analysis of variance and means were compared by the Tukey's test at 5% significance. The curves concerning the emergence percentage over time were fit by the logistic growth equation for each treatment and the means of each parameter (A, B, C) were compared by the Duncan's test at 5% significance. The substrates vermiculite led to the highest values of emergence percentage differing from the PlantMax® Citrus, but not of the coconut fiber, however the vermiculite promoted seedling height in a shorter time; therefore, this substrate is recommended for the initial development of "araticum-de-terra-fria" (Annona emarginata (Schltdl.) H. Rainer) seedlings.

Neutralization of (NK-cell-derived) B-cell activating factor by Belimumab restores sensitivity of chronic lymphoid leukemia cells to direct and Rituximab-induced NK lysis.

Natural killer (NK) cells are cytotoxic lymphocytes that substantially contribute to the therapeutic benefit of antitumor antibodies like Rituximab, a crucial component in the treatment of B-cell malignancies. In chronic lymphocytic leukemia (CLL), the ability of NK cells to lyse the malignant cells and to mediate antibody-dependent cellular cytotoxicity upon Fc receptor stimulation is compromised, but the underlying mechanisms are largely unclear. We report here that NK-cells activation-dependently produce the tumor necrosis factor family member 'B-cell activating factor' (BAFF) in soluble form with no detectable surface expression, also in response to Fc receptor triggering by therapeutic CD20-antibodies. BAFF in turn enhanced the metabolic activity of primary CLL cells and impaired direct and Rituximab-induced lysis of CLL cells without affecting NK reactivity per se. The neutralizing BAFF antibody Belimumab, which is approved for treatment of systemic lupus erythematosus, prevented the effects of BAFF on the metabolism of CLL cells and restored their susceptibility to direct and Rituximab-induced NK-cell killing in allogeneic and autologous experimental systems. Our findings unravel the involvement of BAFF in the resistance of CLL cells to NK-cell antitumor immunity and Rituximab treatment and point to a benefit of combinatory approaches employing BAFF-neutralizing drugs in B-cell malignancies.