Synthesis of isomeric 3-piperidinyl and 3-pyrrolidinyl benzo[5,6]cyclohepta[1,2-b]pyridines: sulfonamido derivatives as inhibitors of Ras prenylation

Blocking farnesylation of oncogenic Ras proteins is a mechanism based therapeutic approach that is of current interest for the development of antitumor agents to treat ras associated tumors. As part of a SAR study on the lead farnesyl protein transferase (FPT) inhibitor I, we report here the synthesis of novel geometric isomers II and III and the FPT inhibition activity of their N-acyl and N-sulfonamido derivatives 15-65. The N-acyl derivatives are markedly less active than the lead inhibitor I thereby demonstrating that the spatial location of the N-acyl group in I is critical for binding of the compound to FPT. In contrast to I, the N-sulfonamido-II series is a novel lead of non-sulfhydryl, nonpeptidic compounds that are dual FPT/GGPT inhibitors. In light of recent reports on the alternative prenylation of N- and K-Ras, dual FPT/GGPT inhibitors may be required to control cell proliferation in tumors containing activated Ras.     

Filipino personality structure and the big five model: a lexical approach

In lexically based studies, we derived Filipino personality dimensions and related them to the Big Five model. In Study 1, Filipino high-school and college students (N = 629) rated themselves on a near-comprehensive list of 861 Filipino (Tagalog) trait adjectives. In Study 2, Filipino high-school and college students (N = 1,531) rated 280 markers of dimensions identified in Study 1. Some students (n = 473) also completed the NEO Five-Factor Inventory. Seven comparable Filipino dimensions were identified in factor analyses in the two studies. We concluded that the dimensions we labeled Concern for Others (vs. Egotism), Conscientiousness, Gregariousness, and Intellect were quite similar to Big Five Agreeableness, Conscientiousness, Extraversion, and Intellect, respectively. The Filipino Self-Assurance dimension was most similar to Big Five Neuroticism. The Filipino Temperamentalness dimension was more complex in Big Five terms, overlapping Agreeableness, Conscientiousness, and Neuroticism. A final Filipino factor resembled a Negative Valence or Infrequency dimension. More than five factors had to be extracted to obtain Philippine dimensions resembling all of the Big Five.     

An universal model of health and work output: theoretical structure and testing strategy

The model proposed in this paper presents a broad range of factors to predict individual human work output. The predictors include aerobic capacity, body size, motivation, work pattern, social environment and social network, caloric intake, drug and alcohol use, stress resistance and thermoregulation. Health is a major intervening variable, and its relationship to work output is a special concern of this research. We suggest that this model may be used as a template to explain human productivity in most societies. Its universality can be subjected to rigorous testing in a range of settings from tropical upland swidden horticulturalists to urban workers in a northern industrialized country. Observations are offered on some of those testing sites and on methodological issues implicit in research of this breadth. A major pilot study of urban Chinese workers has already demonstrated the predictive power of the model in one setting.     

Paleomagnetic evidence of a low-temperature origin of carbonate in the Martian meteorite ALH84001

Indirect evidence for life on Mars has been reported from the study of meteorite ALH84001. The formation temperature of the carbonates is controversial; some estimates suggest 20 degrees to 80 degrees C, whereas others exceed 650 degrees C. Paleomagnetism can be used to distinguish between these possibilities because heating can remagnetize ferrimagnetic minerals. Study of two adjacent pyroxene grains from the crushed zone of ALH84001 shows that each possesses a stable natural remanent magnetization (NRM), implying that Mars had a substantial magnetic field when the grains cooled. However, NRM directions from these particles differ, implying that the meteorite has not been heated significantly since the formation of the internal crushed zone about 4 billion years ago. The carbonate globules postdate this brecciation, and thus formed at low temperatures.     

Tension pneumothorax precluding laparoscopic repair of diaphragmatic hernia

BACKGROUND: Central Europe and the Czech Republic are specific in the prevalence of obesity which has increased by 10-40% during the last 10 years. METHODS: In the Czech republic there is 30 years of experience of a comprehensive approach to obesity treatment which includes: dietary treatment; exercise; behavioral modification; drug treatment; and bariatric surgery. Each of these approaches has its place in complex obesity management. Since 1983 bariatric surgery has been established in the Czech Republic for the treatment of morbid obesity. Vertical banded gastroplasty (VBG), gastric banding, laparoscopic nonadjustable and adjustable gastric bandings have been used over the years. Since 1993 laparoscopic gastric banding has been the only method used in our department. RESULTS: The comprehensive approach for obesity treatment in the Czech Republic has resulted in the development of obesity management and research centers, regional obesity units, obesity out-patients clinics and weight reduction clubs. The surgical treatment is a well-established part of this system and the long-term results of surgical treatment are acceptable both in terms of weight loss and complication rate. There has been no statistical difference in weight loss results following VBG and laparoscopic gastric banding, but there is a significant decrease in morbidity, and shorter hospital stay associated with laparoscopic gastric banding. CONCLUSIONS: The surgical approach in obesity treatment has an important place in the comprehensive care of obese patients. Laparoscopic gastric banding in the hands of an experienced surgeon is a method with low morbidity, short hospital stay and long-term weight loss results which are fully comparable with the results of other surgical approaches.     

Identification of Additional Volatile Compounds from Cbntaloupe

The volatile components of cantaloupe pericarp were analyzed during ripening by gas-liquid chromatography-mass spectrometry. Thirty-two compounds were identified from concentrates prepared by steam distillation-solvent extraction of the volatiles. Eight of the constituents including ethyl (methylthio) acetate, (Z)-6-nonenyl acetate, (Z, Z)-3,6-nonadienyl acetate, benzyl propionate, benzyl alcohol, a sesquiterpene hydrocarbon, cinnamyl acetate and an isomer of 3,4-dimethoxyacetophenone have not been identified previously. Headspace analysis of cantaloupe samples at six stages of maturity showed increases in total ethyl and acetate esters, acetaldehyde, ethyl acetate, and ethanol with maturation. Levels of these compounds remained low and relatively constant until the breaker stage and thereafter increased rapidly until the fruit was fully mature.