The ability of the rat to metabolize myristoyl-methionine: an acylamino acid with potentially useful antibacterial properties

Two experiments with Sprague Dawley rats tested their ability to hydrolyse myristoyl-methionine (M-M) into myristic acid and L-methionine (M). In the first experiment, lasting for 3 days. male rats were orally administered [9,10-3H]myristoyl-L-[35S]methionine. The recovery of radioactivity was approximately 90% for both isotopes; 19% of the administered 3H was recovered in the urine and 16% in the faeces, while the recovered 35S activity was 13 and 12%, respectively. The balance of the radioactivity was found among the tissues, organs and blood. In the second experiment, male and female rats received soybean-based diets which were supplemented with either 0.305% M-M or 0.2% M (both diets contained equal amounts of M) for periods up to 4 weeks. The growth rate of the rats receiving the 0.305% M-M diets was slightly slower than that for the rats on the 0.2% M diet, but the difference was not statistically significant (P > 0.05). The M-M rats had a transitory decrease in feed consumption, suggesting that palatability may have contributed to the growth difference and that a somewhat greater amount of M-M was necessary for the rat to attain the same growth rate as that produced by 0.2% M. When the amount of dietary M-M was increased to 3.05% M-M, a greater reduction in feed consumption and body weight gain was observed. This latter diet was an initial attempt to study the potential toxicity of M-M. None of the haematological, clinical chemistry or organ weight data suggested that M-M was overtly toxic per se, but longer-term feeding studies are needed to evaluate the potential toxicity of M-M more fully.     

Interleukin 8 (IL-8) induces the expression of kinin B1 receptor in human lung fibroblasts

Near-haploidy is a rare cytogenetic finding in childhood acute lymphoblastic leukaemia (ALL) and is associated with a poor prognosis. A second hyperdiploid line, occurring presumably by endoreduplication of the near-haploid stemline, is often observed. We present a case of common ALL in relapse characterized morphologically by a dual population of small and large lymphoblasts. Cytogenetic analysis supplemented with fluorescence in-situ hybridization (FISH) studies localized near-haploidy and hyperdiploidy to the small and large blast population respectively. DNA ploidy determination confirmed two abnormal clones with near-haploidy as the predominant one. A novel t(9;12)(q11;q13) was present in the near-haploid clone and was duplicated in the hyperdiploid clone. This finding identified cells bearing near-haploidy to be the clonogenic population following malignant transformation and confirmed endoreduplication as the mechanism for the presence of associated hyperdiploidy.     

Finance and the technology-trade nexus

This paper sketches the contours of the evolving international/monetary system and examines the various roles of the intemediation mechanisms. Then it examines the extent to which the financial system is independent from the “real economy” and the various ways in which it impacts it. The paper discusses some views in good currency on the dynamics of the technology-trade-finance nexus and shows how the financial system influences organization, location and technology choices in meso-innovation systems. The final section of the paper looks at the policy implications that might be derived from the analysis and suggests some directions for the future research.     

Gelatinases in drug-induced toxic epidermal necrolysis

BACKGROUND: The matrix metalloproteinases (MMPs) MMP2 and MMP9 play a significant role in epidermal detachment, inflammation and re-epithelialization. We have evaluated their activity in toxic epidermal necrolysis (TEN). DESIGN: The level and pattern of activity of MMP2 and MMP9 were investigated by measuring the degradation of 3H-labelled gelatin and by zymography in blister fluid from six TEN patients and compared the results with three other blistering conditions: bullous pemphigoid (n = 6), second-degree burn (n = 13) or suction blister (n = 3). RESULTS: A higher amount of MMP2 was found in TEN blister fluid with the constant presence of a significantly larger proportion of the activated forms of MMP2, a particular feature of TEN, than the other blistering diseases studied. CONCLUSION: This study emphasizes the potential role of MMP2 in the specific inflammatory reaction and reparation process in TEN skin.     

Physical ergonomic hazards in highway tunnel construction: overview from the Construction Occupational Health Program

This report provides an overview of physical ergonomic exposures in highway construction work across trades and major operations. For each operation, the observational method “PATH” (Posture, Activity, Tools and Handling) was used to estimate the percentage of time that workers spent in specific tasks and with exposure to awkward postures and load handling. The observations were carried out on 73 different days, typically for about 4 h per day, covering 120 construction workers in 5 different trades: laborers, carpenters, ironworkers, plasterers, and tilers. Non-neutral trunk postures (forward or sideways flexion or twisting) were frequently observed, representing over 40% of observations for all trades except laborers (28%). Kneeling and squatting were common in all operations, especially tiling and underground utility relocation work. Handling loads was frequent, especially for plasterers and tilers, with a range of load weights but most often under 15 pounds. The results of this study provide quantitative evidence that workers in highway tunnel construction operations are exposed to ergonomic factors known to present significant health hazards. Numerous opportunities exist for the development and implementation of ergonomic interventions to protect the health and safety of construction workers.     

Unsupervised writer adaptation applied to handwritten text recognition

This paper deals with the problem of off-line handwritten text recognition. It presents a system of text recognition that exploits an original principle of adaptation to the handwriting to be recognized. The adaptation principle is based on the automatic learning, during the recognition, of the graphical characteristics of the handwriting. This on-line adaptation of the recognition system relies on the iteration of two steps: a word recognition step that allows to label the writer's representations (allographs) on the whole text and a re-evaluation step of character models. Tests carried out on a sample of 15 writers, all unknown by the system, show the interest of the proposed adaptation scheme since we obtain during iterations an improvement of recognition rates both at the letter and the word levels.     

The PKR/P38/RIPK1 Signaling Pathway as a Therapeutic Target in Alzheimer’s Disease

Neuropathological lesions in Alzheimer’s disease (AD) include amyloid plaques formed by the accumulation of amyloid peptides, neurofibrillary tangles made of hyperphosphorylated tau protein, synaptic and neuronal degenerations, and neuroinflammation. The cause of AD is unknown, but according to the amyloid hypothesis, amyloid oligomers could lead to the activation of kinases such as eukaryotic translation initiation factor 2-alpha kinase 2 (PKR), p38, and receptor-interacting serine/threonine-protein kinase 1 (RIPK1), which all belong to the same stress-activated pathway. Many toxic kinase activations have been described in AD patients and in experimental models. A p38 mitogen-activated protein kinase inhibitor was recently tested in clinical trials but with unsuccessful results. The complex PKR/P38/RIPK1 (PKR/dual specificity mitogen-activated protein kinase kinase 6 (MKK6)/P38/MAP kinase-activated protein kinase 2 (MK2)/RIPK1) is highly activated in AD brains and in the brains of AD transgenic animals. To delineate the implication of this pathway in AD, we carried out a search on PubMed including PKR/MKK6/p38/MK2/RIPK1, Alzheimer, and therapeutics. The involvement of this signaling pathway in the genesis of AD lesions, including Aβ accumulations and tau phosphorylation as well as cognitive decline, is demonstrated by the reports described in this review. A future combination strategy with kinase inhibitors should be envisaged to modulate the consequences for neurons and other brain cells linked to the abnormal activation of this pathway.     

Decarboxylative Heterocoupling Coupling of Substituted Benzoic Acids for Biaryl Synthesis

The heterocoupling between 2-nitrobenzoic and 2,6-dimethoxybenzoic acids was studied. It was demonstrated that the [PdCl₂/Cu(OH)₂:0.2/0.75 equiv.] catalytic system can catalyze this reaction with significant yield. Further optimizations (i.e.: sources and loadings of copper and palladium salts, base) allowed to isolate the biaryl in 70 % yield. A catalytic cycle that accounts for the observed results is proposed. While the bi-metal catalyst has shown high yields with some substrates, it is only able to catalyze the decarboxylative coupling in high yield for some of the substrates studied.     

The ability of limited exposure sampling to detect effects of interventions that reduce the occurrence of pronounced trunk inclination

Ergonomics interventions often focus on reducing exposure in those parts of the job having the highest exposure levels, while leaving other parts unattended. A successful intervention will thus change the form of the job exposure distribution. This disqualifies standard methods for assessing the ability of various exposure measurement strategies to correctly detect an intervention's effect on the overall job exposure of an individual worker, in particular for the safety or ergonomics practitioner who with limited resources can only collect a few measurements. This study used a non-parametric simulation procedure to evaluate the relationship between the number of measurements collected during a self-paced manufacturing job undergoing ergonomics interventions of varying effectiveness, and the probability of correctly determining whether and to which extent the interventions reduced the overall occurrence of pronounced trunk inclination, defined as an inclination of at least 20°. Sixteen video-recordings taken at random times on multiple days for each of three workers were used to estimate the time distribution of each worker's exposure to pronounced trunk inclination. Nine hypothetical ergonomics intervention scenarios were simulated, in which the occurrence of pronounced trunk inclination in the upper 1/8, 1/4, and 1/2 of the job exposure distribution was reduced by 10%, 30% and 50%. Ten exposure measurement strategies were explored, collecting from one to ten pre- and post-intervention exposure samples from an individual worker. For each worker, intervention scenario and sampling strategy, data were bootstrapped from the measured (pre-intervention) and simulated (post-intervention) exposure distributions to generate empirical distributions of the estimated intervention effect. Results showed that for the one to three intervention scenarios that had the greatest effect on the overall occurrence of trunk inclination in the job, one to four pre- and post-intervention measurements, depending on worker, were sufficient to reach an 80% probability of detecting that the intervention did, indeed, have an effect. However, even for the intervention scenario that had the greatest effect on job exposure, seven or more samples were needed for two of the three workers to obtain a probability larger than 50% of estimating the magnitude of the intervention effect to within ±50% of its true size. For almost all interventions affecting 1/8 or 1/4 of the job, limited exposure sampling led to low probabilities of detecting any intervention effect, let alone its correct size.     

On the identification of time-invariant discrete processes

An identification procedure for determination of coefficients of pulse transfer function is proposed. This procedure is applicable for the case when measurement noises of input and output are independent of input to a process and the variances of the noises are known only in the form of the ratio. The noises can be colored. The criterion used for identification is given by extending the mean-square equation error. The optimal estimates are obtained from the eigenvector of a linear operator which corresponds to the least eigenvalue. The theoretical analysis is given and the direction for the practical usage is suggested to use the least-square error criterion.