Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Befloxatone, a Reversible Selective Monoamine Oxidase‐A Inhibitor, on Psychomotor Function and Memory in Healthy Subjects

Befloxatone is a new reversible and selective monoamine oxidase (MAO‐A) inhibitor that has been shown to have antidepressant activity in various animal models. To assess the effects of single oral doses of befloxatone (5, 10, and 20 mg) on psychomotor performance and memory, a randomized, double‐blind, five‐way, crossover study with both placebo and amitriptyline (50 mg) was carried out in 15 healthy male volunteers. Psychomotor and cognitive functions were evaluated using both objective measures, including Critical Flicker Frequency (CFF), Choice Reaction Time (CRT), Digit Symbol Substitution Test (DSST), and a picture memory test, and subjective measures, including Visual Analog Scales (VAS) and Addiction Research Center Inventory (ARCI), before and 2, 4, and 8 hours after administration. Pupil diameter was recorded by videopupillography. Single doses of befloxatone from 5 to 20 mg did not result in any detrimental effects on skilled performance and memory. In contrast, amitriptyline significantly impaired arousal (CFF), speed of reaction (CRT), information processing (DSST) and long‐term memory (delayed free recall of pictures) and produced subjective sedation from 2 to 8 hours after administration. At the doses studied amitriptyline induced miosis but befloxatone did not modify pupil diameter. There was no evidence in this study to suggest that befloxatone, at the doses studied, has any sedative or amnesic effects in healthy subjects.
Modulation of H+ Transport Mechanisms by Interleukin-1 in Isolated Bovine Articular Chondrocytes

The proinflammatory cytokine interleukin-1 (IL-1) promotes the degradation of articular cartilage by inhibiting matrix synthesis and stimulating degradative enzyme activity. Generation of nitric oxide (NO) in response to IL-1 is implicated in these actions. The catabolic actions of IL-1 can be inhibited by manoeuvres which are predicted to dissipate H+ gradients across the chondrocyte plasma membrane. In the present study, the effects of IL-1 on H+ extrusion from bovine articular chondrocytes were investigated. pH was measured using the H+-sensitive fluorescent dye BCECF. Cells were acidified by ammonium rebound and the contribution of the Na+-H+ exchanger (NHE) and of the vacuolar H+-ATPase to acid extrusion was characterised by ion substitution and inhibitor studies. Overnight (18h) exposure to IL-1 stimulated acid extrusion in a dose-dependent fashion. This effect represented stimulation of both NHE and the ATPase. Characterisation of the timecourse of this response indicated that, while stimulation of acid extrusion was rapid, effects on the ATPase were only apparent after greater than 8h incubation with the cytokine. In keeping with this observation, the protein synthesis inhibitor cycloheximide abolished the stimulatory effect of IL-1 on ATPase-mediated extrusion. The upregulation of ATPase activity by IL-1 was inhibited by the NOS inhibitor L-NAME and by the NO scavenger PTIO. In cells which had not been exposed to IL-1, treatment with the NO donor SNAP also stimulated acid extrusion by the ATPase. In contrast, NHE activity was not altered by any of these compounds. Taken together, these results imply that IL-1 can stimulate acid extrusion in chondrocytes and that this reflects rapid upregulation of NHE with slower induction of H+-ATPase activity which requires elevated levels of NO. While ATPase induction involves protein synthesis, this process may not constitute synthesis of ATPase proteins per se, but rather of some associated regulatory process.
Single molecule protein biophysics using chemically modified nanopores

The kinetics of protein folding and binding are not only scientifically relevant to understanding the complex molecular machine-like functionality of proteins inside of cells but can also help elucidate disease pathways and lead to better therapeutic agents. Using nanopores to investigate these kinetics holds great potential for such proteomic studies in which the structure and function of proteins can be rapidly screened. In this study, we achieve part of this goal by detecting the folded and unfolded states of BSA. Furthermore, we also show that protein sensing can be performed on more biologically significant protein domains such as PDZ2. To achieve this goal, pore fabrication methods and chemical surface modifications were investigated and optimized for efficient protein sensing.
Interphotoreceptor retinoid–binding protein removes all-trans-retinol and retinal from rod outer segments, preventing lipofuscin precursor formation

Interphotoreceptor retinoid–binding protein (IRBP) is a specialized lipophilic carrier that binds the all-trans and 11-cis isomers of retinal and retinol, and this facilitates their transport between photoreceptors and cells in the retina. One of these retinoids, all-trans-retinal, is released in the rod outer segment by photoactivated rhodopsin after light excitation. Following its release, all-trans-retinal is reduced by the retinol dehydrogenase RDH8 to all-trans-retinol in an NADPH-dependent reaction. However, all-trans-retinal can also react with outer segment components, sometimes forming lipofuscin precursors, which after conversion to lipofuscin accumulate in the lysosomes of the retinal pigment epithelium and display cytotoxic effects. Here, we have imaged the fluorescence of all-trans-retinol, all-trans-retinal, and lipofuscin precursors in real time in single isolated mouse rod photoreceptors. We found that IRBP removes all-trans-retinol from individual rod photoreceptors in a concentration-dependent manner. The rate constant for retinol removal increased linearly with IRBP concentration with a slope of 0.012 min−1 μm−1. IRBP also removed all-trans-retinal, but with much less efficacy, indicating that the reduction of retinal to retinol promotes faster clearance of the photoisomerized rhodopsin chromophore. The presence of physiological IRBP concentrations in the extracellular medium resulted in lower levels of all-trans-retinal and retinol in rod outer segments following light exposure. It also prevented light-induced lipofuscin precursor formation, but it did not remove precursors that were already present. These findings reveal an important and previously unappreciated role of IRBP in protecting the photoreceptor cells against the cytotoxic effects of accumulated all-trans-retinal.
Caracterização morfológica do fruto, da semente e desenvolvimento pós-seminal do abacateiro

Resumo A propagacao do abacateiro e comercialmente, realizada por enxertia da variedade desejada sobre porta-enxertos seminais. No entanto, a literatura e discordante sobre a ocorrencia de poliembrionia e tipo de fruto, nesta especie. Em funcao do exposto, o trabalho objetivou caracterizar o tipo de fruto, aspectos morfologicos da semente e da plântula, alem de avaliar o numero de embrioes existente. O abacateiro possui frutos do tipo baga, as sementes sao monoembrionicas e exalbuminosas, a germinacao e hipogea e a emergencia das plântulas ocorreu 33 dias apos a semeadura. A raiz primaria e longa e de coloracao branca e as raizes secundarias sao curtas e filiformes. Os cotiledones sao macicos e de coloracao rosada. Foi possivel observar a presenca de multiplos cauliculos na semente de abacate, originados do colo. As sementes apresentam policaulia; o inicio da estabilizacao da emergencia de plântulas ocorreu na oitava semana, sendo inviavel para a propagacao da especie, manter essas sementes no viveiro por mais tempo.
Stopped Delta -matter source in heavy-ion collisions at 10 GeV/nucleon?

We predict the formation of highly dense baryon-rich resonance matter in Au+Au collisions at AGS energies. The final pion yields show observable signs for resonance matter. The Delta(1232) resonance is predicted to be the dominant source for pions of small transverse momenta. Rescattering effects -- consecutive excitation and deexcitation of Deltas -- lead to a long apparent lifetime (> 10 fm/c) and rather large volumina (several 100 fm^3) of the Delta-matter state. Heavier baryon resonances prove to be crucial for reaction dynamics and particle production at AGS.
Prediction of Recurrence After Radical Surgery for Gastric Cancer: A Scoring System Obtained From a Prospective Multicenter Study

Objective:The aim of this prospective multicenter study was to define a scoring system for the prediction of tumor recurrence after potentially curative surgery for gastric cancer. Summary Background Data:The estimation of the risk of recurrence in individual patient may be relevant in clinical practice, to apply adjuvant therapies after surgery, and plan an adequate follow-up program. Only a few studies, most of which were retrospective or performed on a limited number of patients, have developed a prognostic score in patients with gastric cancer. Methods:A total of 536 patients who underwent UICC R0 resection between 1988 and 1998 at 3 surgical departments in Italy were considered. All patients were followed up using a standard protocol after discharge from the hospital. The mean follow-up period was 56 ± 44 months, and 94 ± 29 months for surviving patients. The scoring system was calculated on the basis of a logistic regression model, where the presence of the recurrence was the dependent variable, and clinicopathologic variables were the covariates. Results:Recurrence occurred in 272 of 536 patients (50.7%). The scoring system for the prediction of the risk in individual cases gave values ranging from 1.4 to 99.9; the model distributed most cases in the extremes of the range. The risk of recurrence increased remarkably with score values; it was only 5% in patients with a score below 10, up to 95.4% in patients with a score of 91 to 100. No recurrence was observed in 43 patients with a score below 4, whereas all of the 56 patients with a score over 97 presented a recurrence. The model correctly predicted recurrence in 227 of 272 patients (sensitivity, 83.5%), whereas the absence of recurrence was correctly predicted in 214 of 264 patients (specificity, 81.1%); the overall accuracy was 82.2%. Prognostic score was clearly superior to UICC tumor stage in predicting recurrence. The high effectiveness of the score was confirmed in preliminary data of a validation study. Conclusions:The scoring system obtained with a regression model on the basis of our follow-up data is useful for defining subgroups of patients at a very low or very high risk of tumor recurrence after radical surgery for gastric cancer. Final results of the validation study are essential for a clinical application of the model.
Protective role of selenium supplementation against cardiac lesions induced by the combination of levomepromazine and risperidone in the rabbit

Neuroleptics are a suspected cause of sudden death in psychiatric patients, especially in those with pre-existing cardiac lesions. As these lesions were previously shown to be associated with selenium (Se) deficiency, the aim of the present study was to evidence the possible protective effect of Se supplementation against cardiac lesions induced by the combination of the neuroleptic drugs levomepromazine and risperidone in the rabbit. Two groups of 6 rabbits were treated with 3 mg/kg of levomepromazine daily intramuscularly combined with 1 mg/kg of risperidone intramuscularly every other week for 3 consecutive months, and one group additionally received a solution of sodium selenite (2 μg/kg/day) intramuscularly during the whole treatment period. Furthermore, one group of six untreated animals was given the Se supplementation and another group of six control animals received saline daily. Blood samples were drawn before and at the end of the treatment period for the measurement of serum Se levels. At the end of the study, all animals were sacrificed and their hearts were removed for the measurement of tissue Se concentrations. In addition, the hearts were prepared for histopathological examination. A variety of cardiac lesions was found in the neuroleptics-treated animals without supplementation and to a lesser extent in the control and Se-supplemented untreated animals. Importantly, only rare cardiac lesions were observed in neuroleptics-Se-treated animals. The most striking differences in Se concentrations were noted in the myocardium: as compared to controls, there was a 43% reduction in neuroleptics-treated, but non-Se-supplemented animals (p < .01), at the end of the treatment period, whereas only a 14% reduction (p < .05) was noted in the neuroleptics-Se-treated animals. These results confirm that neuroleptics induce cardiac lesions associated with Se deficiency. Selenium supplementation markedly decreased the incidence and severity of neuroleptics-induced cardiac lesions and these findings may serve as a basis for further evaluation of the protective role of Se supplementation in neuroleptics-treated patients. However, Se supplementation in normal animals without Se deficiency was also shown to be cardiotoxic.
Inhibition of ameloblastoma invasion in vitro and in vivo by inhibitor of metalloproteinase-2 activity.

BACKGROUND Ameloblastoma is an odontogenic benign tumor characterized by local invasiveness and most of its local recurrences clinically result from local invasion. This study used matrix metalloproteinase-2 (MMP-2) inhibitor I (MMP-2I) to investigate the role played by MMP-2 activity in the local invasiveness of ameloblastoma. METHODS The cells and xenografts of ameloblastoma were treated with MMP-2I and treatment group were compared with the control group. In vitro, the invasive activity of tumor cells was assayed in transwell cell culture chamber. Gelatinolytic activity of gelatinases and MMP-2/tissue inhibitor of matrix metalloproteinase (TIMP-2) protein expression was detected using gelatin zymography and flow cytometry. The cell viability and adhesion were evaluated using methyl thiazol tetrazolium. In vivo, bilateral subrenal capsule xenograft transplantation of ameloblastoma was performed in 10 nude mice and the invasion of ameloblastoma into the renal parenchyma was observed. RESULTS Active-MMP-2 of conditioned media was significantly lower in treatment group than in the control group. Accordingly, potential of in vitro cell invasion, adhesion and in vivo tumor invasion were also significantly lower in the treatment group than in the control group. CONCLUSIONS Inhibitor of MMP-2 activity suppressed the local invasive capability of ameloblastoma by decreasing MMP-2 activity. MMP-2 activity is in relation with invasive capacity of ameloblastoma.
Dissociable Neural Activations of Conscious Visibility and Attention

Recent neuroimaging evidence indicates that visual consciousness of objects is reflected by the activation in the lateral occipital cortex as well as in the frontal and parietal cortex. However, most previous studies used behavioral paradigms in which attention raised or enhanced visual consciousness (visibility or recognition performance). This co-occurrence made it difficult to reveal whether an observed cortical activation is related to visual consciousness or attention. The present fMRI study investigated the dissociability of neural activations underlying these two cognitive phenomena. Toward this aim, we used a visual backward masking paradigm in which directing attention could either enhance or reduce the object visibility. The participants' task was to report the level of subjective visibility for a briefly presented target object. The target was presented in the center with four flankers, which was followed by the same number of masks. Behavioral results showed that attention to the flankers enhanced the target visibility, whereas attention to the masks attenuated it. The fMRI results showed that the occipito-temporal sulcus increased activation in the attend flankers condition compared with the attend masks condition, and occipito-temporal sulcus activation levels positively correlated with the target visibility in both attentional conditions. On the other hand, the inferior frontal gyrus and the intraparietal sulcus increased activation in both the attend flankers and attend masks compared with an attend neither condition, and these activation levels were independent of target visibility. Taken together, present results showed a clear dissociation in neural activities between conscious visibility and attention.
Temporal Finitude and Finitude of Possibility: The Double Meaning of Death in Being and Time

Abstract The confusion surrounding Heidegger’s account of death in Being and Time has led to severe criticisms, some of which dismiss his analysis as incoherent and obtuse. I argue that Heidegger’s critics err by equating Heidegger’s concept of death with our ordinary concept. As I show, Heidegger’s concept of death is not the same as the ordinary meaning of the term, namely, the event that ends life. But nor does this concept merely denote the finitude of Dasein’s possibilities or the groundlessness of existence, as William Blattner and Hubert Dreyfus have suggested. Rather, I argue, the concept of death has to be understood both as temporal finitude and as finitude of possibility. I show how this reading addresses the criticisms directed at Heidegger’s death analysis as well as solving textual problems generated by more limited interpretations of the concept.
Solution of the von Mises Boundary Layer Equation Using a High-Speed Computer

dz d2Z On the plate, —= —2(1 — x) and u is zero and so from (1), —is infinite. This ox dyf/2 unpleasant singularity on the plate caused Görtier [1] to abandon finite difference methods of solution of the von Mises equation and it looked as if the comparative simplicity of ( 1 ) could never be utilized from the point of view of numerical solution. Thomson and the present author [2], however, showed that finite difference solutions are possible using the von Mises equation and obtained the expansion
Neonicotinoid concentrations in arable soils after seed treatment applications in preceding years.

BACKGROUND Concentrations of the neonicotinoid insecticides clothianidin, thiamethoxam and imidacloprid were determined in arable soils from a variety of locations in England. RESULTS In soil samples taken from the central area of fields, concentrations of clothianidin ranged from 0.02 to 13.6 µg kg(-1) . Thiamethoxam concentrations were between <0.02 and 1.50 µg kg(-1) , and imidacloprid concentrations between <0.09 and 10.7 µg kg(-1) . Concentrations of clothianidin and thiamethoxam were lower in soil samples taken from the edges of fields than from the centres of fields, but this difference was less pronounced for imidacloprid. CONCLUSION This work gives a clear indication of the levels of neonicotinoids in arable soils after typical use of these compounds as seed dressings in the United Kingdom. There was evidence that imidacloprid was more persistent in the soils studied than clothianidin and thiamethoxam. As clothianidin and thiamethoxam have largely superseded imidacloprid in the United Kingdom, neonicotinoid levels were lower than suggested by predictions based on imidacloprid alone.
Chance Variation: Darwin on Orchids

How, according to Darwin, does chance variation affect evolutionary outcomes? In his 1866 book, On the Various Contrivances by which British and Foreign Orchids are Fertilised by Insects, Darwin developed an argument that played an important role in his overall case for evolution by natural selection, as articulated in later editions of the Origin. This argument also figured significantly in Darwin's reflections on the theological dimensions of evolution by natural selection.
Small-scale mechanical testing of materials

Small-scale mechanical testing of materials has gained prominence in the last decade or so due to the continuous miniaturization of components and devices in everyday application. This review describes the various micro-fabrication processes associated with the preparation of miniaturized specimens, geometries of test specimens and the small scale testing techniques used to determine the mechanical behaviour of materials at the length scales of a few hundred micro-meters and below. This is followed by illustrative examples in a selected class of materials. The choice of the case studies is based on the relevance of the materials used in today's world: evaluation of mechanical properties of thermal barrier coatings (TBCs), applied for enhanced high temperature protection of advanced gas turbine engine components, is essential since its failure by fracture leads to the collapse of the engine system. Si-based substrates, though brittle, are indispensible for MEMS/NEMS applications. Biological specimens, whose response to mechanical loads is important to ascertain their role in diseases and to mimic their structure for attaining high fracture toughness and impact resistance. An insight into the mechanisms behind the observed size effects in metallic systems can be exploited to achieve excellent strength at the nano-scale. A future outlook of where all this is heading is also presented.
Smallholder dairy value chain development: The case of Ada’a woreda, Oromia Region, Ethiopia

In the past decades, public sector support for dairy development in Ada’a mainly focused on dairy production and supply of inputs/services, with limited involvement of the private sector and partners. There was also no clear distinction between the dairy system development potentials in urban, peri-urban and rural areas. With the help of a participatory commodity value chain development approach, introduced by the IPMS project, the Ada’a Office of Agriculture managed to address some of these issues in the peri-urban dairy production system. Training, including sharing of knowledge with experienced farmers and follow-up events, especially field days, was used to build capacity of extension staff and farmers. This has helped to promote linkages between producers and input suppliers/service providers. With the help of Ada’a Dairy Cooperative and the Cooperatives Promotion Office, it was possible to organize collective action for marketing of fluid milk by diary producers in three peri-urban locations. Production of backyard fodder was successfully linked to 143 peri-urban farmers involved in commercial livestock production. The artificial insemination (AI) service delivery system during the project’s life changed from public sector dominated system in 2005 (100%) to a private sector dominated system in 2010 (98%). Still considerable efforts need to be made to further improve the effectiveness and efficiency of the system, while the recently IPMS-introduced hormone assisted mass insemination approach should be further explored, especially since pregnancy rates improved by 100%. As a result of increased demand for dairy products in Addis Ababa and other major urban centres, many more private agribusinesses for supply of inputs and processing of milk established themselves in Ada’a, which can be instrumental in leading development. Government can and should increase its capacity to develop, promote and regulate these new actors to ensure quality of services/inputs and processed products. The impact study conducted by the project in the peri-urban system showed that in 2010 annual gross production value from fluid milk reached over three million Ethiopian birr (ETB)1, a fiftyfold increase. Annual income/household also increased from less than ETB 1000 in 2005/06 to ETB 19,000 in 2010.