The season‐of‐birth paradox

Abstract

Vital statistics data show a remarkably consistent seasonality in U.S. birth patterns, with peaks in late summer and winter months, and a valley in the spring. An attitude survey of college students suggests that peaks in the actual birth distribution occur in unpopular months in which to give birth; the valley in the actual birth distribution occurs in popular months. This paradoxical finding is named the Season‐of‐Birth Paradox. Explanations to resolve the paradox include biological and psychological components. A psychological mechanism—named the Misinformed Reproducer Hypothesis—is tested using NSFG data from the 1973–75 and 1979–81 cycles. Results suggest that women stop contracepting with the expectation that they will get pregnant almost immediately. When it takes several months on the average for a successful conception to occur, the actual birth distribution is shifted away from the preferred birth distribution. These results suggest that psychological as well as biological mechanisms underlie the consistent seasonality patterns in U.S. births.     

Synthesis of (−)‐DAPD

A new synthesis of (?)‐DAPD, suitable for large scale development, is described.     

Origin of pre‐islamic architecture in West‐Africa

’Cultural theory’, launched by social anthropologist Mary Douglas, has been highly influential in the inter‐disciplinary field concerned with the study of risk perception and risk communication. The theory derives from the grid‐group analyses that Douglas developed in the 1970s. Cultural theory aims to explain universal ‘cultural bias’ by way of a general typology of group formation and a concomitant cosmology or world view. This article critically examines cultural theory and the study of hazards as culturally construed phenomena.     

Alterations of the Characteristics of the Circadian Rest‐Activity Rhythm of Cancer In‐Patients

The aim of the present study was to evaluate the characteristics of the circadian rest‐activity rhythm of cancer patients. Thirty‐one in‐patients, consisting of 19 males and 12 females, were randomly selected from the Regional Cancer Center, Pandit Jawaharlal Nehru Medical College, Raipur, India. The rest‐activity rhythm was studied non‐invasively by wrist actigraphy, and compared with 35 age‐matched apparently healthy subjects (22 males and 13 females). All subjects wore an Actiwatch (AW64, Mini Mitter Co. Inc., USA) for at least 4–7 consecutive days. Fifteen‐second epoch length was selected for gathering actigraphy data. In addition, several sleep parameters, such as time in bed, assumed sleep, actual sleep time, actual wake time, sleep efficiency, sleep latency, sleep bouts, wake bouts, and fragmentation index, were also recorded. Data were analyzed using several statistical techniques, such as cosinor rhythmometry, spectral analysis, ANOVA, Duncan's multiple‐range test, and t‐test. Dichotomy index (I<O) and autocorrelation coefficient (r24) were also computed. The results validated a statistically significant circadian rhythm in rest‐activity with a prominent period of 24 h for most cancer patients and control subjects. Results of this study further revealed that cancer patients do experience a drastic alteration in the circadian rest‐activity rhythm parameters. Both the dichotomy index and r24 declined in the group of cancer patients. The occurrence of the peak (acrophase, Ø) of the rest‐activity rhythm was earlier (p<0.001) in cancer patients than age‐ and gender‐matched control subjects. Results of sleep parameters revealed that cancer patients spent longer time in bed, had longer assumed and actual sleep durations, and a greater number of sleep and wake bouts compared to control subjects. Further, nap frequency, total nap duration, average nap, and total nap duration per 1 h awake span were statistically significantly higher in cancer patients than control subjects. In conclusion, the results of the present study document the disruption of the circadian rhythm in rest‐activity of cancer in‐patients, with a dampening of amplitude, lowering of mean level of activity, and phase advancement. These alterations of the circadian rhythm characteristics could be attributed to disease, irrespective of variability due to gender, sites of cancer, and timings of therapies. These results might help in designing patient‐specific chronotherapeutic protocols.     

Design and synthesis of 4,5,6,7‐tetrahydro‐1H‐1,2‐diazepin‐7‐one derivatives as a new series of Phosphodiesterase 4 (PDE4) inhibitors

Phosphodiesterase 4 (PDE4) inhibitors have attractive therapeutic potential in respiratory, inflammatory, metabolic and CNS disorders. The present work details the design, chemical exploration and biological profile of a novel PDE4 inhibitor chemotype. A diazepinone ring was identified as an under-represented heterocyclic system fulfilling a set of PDE4 structure-based design hypotheses. Rapid exploration of the structure activity relationships for the series was enabled by robust and scalable two/three-steps parallel chemistry protocols. The resulting compounds demonstrated PDE4 inhibitory activity in cell free and cell-based assays comparable to the Zardaverine control used, suggesting potential avenues for their further development.     

Acyclonucleoside Iron Chelators of 1‐(2‐Hydroxyethoxy)methyl‐2‐alkyl‐3‐hydroxy‐4‐pyridinones: Potential Oral Iron Chelation Therapeutics

The method of synthesizing acyclonucleoside iron chelators is both convenient and cost effective compared to that of synthesizing ribonucleoside iron chelators. The X‐ray crystal structural analysis shows that the 2‐hydroxyethoxymethyl group does not affect the geometry of the iron chelating sites. Therefore, the iron binding and removal properties of the acyclonucleoside iron chelators should remain similar to the ribonucleoside iron chelators, which is confirmed by the titration and competition reaction of the acyclonucleoside chelators with iron and ferritin, respectively. The acyclonucleoside iron chelators are more lipophilic with measured n‐octanol and Tris buffer distribution coefficients than ribonucleoside iron chelators.     

Synthesis of D‐Altritol Nucleosides with a 3′‐O‐Tert‐Butyldimethylsilyl Protecting Group

Four D‐altritol nucleosides with a 3′‐O‐tert‐butyldimethylsilyl protecting group are synthesized (base moieties are adenine, guanine, thymine and 5‐methylcytosine). The nucleosides are obtained by ring opening reaction of 1,5:2,3‐dianhydro‐4,6‐O‐benzylidene‐D‐allitol. Optimal reaction circumstances (NaH, LiH, DBU, phase transfer, microwave irridation) for the introduction of the heterocycles are base‐specific. For the introduction of the 3′‐O‐silyl protecting group, long reaction times and several equivalents of tert‐butyldimethylsilyl chloride are needed.     

Synthesis and Biological Evaluation of Novel Apio Nucleosides with Thiazole‐4‐carboxamide and 1,2,4‐Triazole‐3‐carboxamide

In view of biological activities of azole nucleosides and apio‐dideoxynucleoside, novel apio nucleoside analogues (1 and 2) with thiazole and triazole base moiety were synthesized using 2,3‐O‐isopropylidene‐apio‐β‐d‐furanose (3), which was prepared from d‐mannose.     

Synthesis and Antiviral Properties of Arabino and Ribonucleosides of 1,3‐Dideazaadenine, 4‐Nitro‐1, 3‐dideazaadenine and Diketopiperazine

Different arabinosides and ribosides, viz. Ara‐DDA or 9(1‐β‐d‐arabinofuranosyl) 1,3‐dideazaadenine (6), Ara‐NDDP or 9(1‐β‐d‐arabinofuranosyl) 4‐nitro‐1,3‐dideazapurine (7), Ara‐DKP or 1(1‐β‐d‐arabinofuranosyl) diketopiperazine (8), Ribo‐DDA or 9(1‐β‐d‐ribofuranosyl) 1,3‐dideazaadenine (9) and Ribo‐NDDP or 9(1‐β‐d‐ribofuranosyl) 4‐nitro‐1,3‐dideazapurine (10) have been synthesized as probable antiviral agents. The arabinosides have been synthesized using the catalyst TDA‐1 that causes stereospecific formation of β‐nucleosides while a one‐pot synthesis procedure was adopted for the synthesis of the ribonucleosides where β‐anomers were obtained in higher yields. All the five nucleoside analogs have been screened for antiviral property against HIV‐1 (III_B), HSV‐1 and 2, parainfluenza‐3, reovirus‐1 and many others. It was observed that arabinosides had greater inhibitory action than ribosides. The compound 7 or Ara‐NDDP has shown maximum inhibition of HIV‐1 replication than the rest of the molecules with an IC₅₀ of 79.4 µg/mL.     

Thiosugar Nucleosides. Synthesis and Biological Activity of 1,3,4‐Thiadiazole,Thiazoline and Thiourea Derivatives of 5‐Thio‐d‐Glucose

New acylated 5‐thio‐β‐d‐glucopyranosylimino‐disusbstituted 1,3,4‐thiadiazols 8, and 11 were prepared, via spontaneous rearrangements, by cycloaddition of the glycosyl isothiocyanate 2 with the reactive intermediates 1‐aza‐2‐azoniaallene hexachloroantimonates 4 and 6, respectively. Reaction of 2 with aminoacetone or chloroethylamine afforded the acylated 5‐thio‐β‐d‐glucopyranosyl‐4‐imidazoline‐2‐thione nucleoside 16 and glucopyranosylamino‐2‐thiazoline derivative 18, respectively. Deblocking of 8, 11, 17 and 19 furnished the free nucleoside analogues 9, 12, 18 and 20, respectively. Analogously, treatment of 2 with chloroethylamine in the 1:2 ratio afforded the thioureylendisaccharide 21. No in vitro antiviral activity against HIV‐1, HIV‐2, human cytomegallovirus (HMCV), has been found for the new synthesized compounds.     

Degradation of a mixture of high‐molecular‐weight polycyclic aromatic hydrocarbons by a Mycobacterium strain PYR‐1

Mycobacterium sp. PYR‐1, which was previously shown to mineralize several individual polycyclic aromatic hydrocarbons (PAHs), simultaneously degraded phenanthrene, anthracene, fluoranthene, pyrene and benzo[a]pyrene in a six‐component synthetic mixture. Chrysene was not degraded significantly. When provided with a complex carbon source, Mycobacterium sp. PYR‐1 degraded greater than 74% of the total PAH mixture during 6 d of incubation. Mycobacterium sp. PYR‐1 appeared to preferentially degrade phenanthrene. No significant difference in degradation rates was observed between fluoranthene and pyrene. Anthracene degradation was slightly delayed but, once initiated, proceeded at a constant rate. Benzo[a]pyrene was degraded slowly. Degradation of a crude mixture of benzene‐soluble PAHs from contaminated sediments resulted in a 47% reduction of the material in 6 d compared with that of autoclaved controls. Experiments using an environmental microcosm test system indicated that mineralization rates of individual ¹⁴C‐labeled compounds were significantly lower in the mixtures than in equivalent doses of these compounds alone. Mineralization of the complete mixture was estimated conservatively to be between 49.7 and 53.6% and was nearly 50% in 30 d of incubation when all compounds were radiolabeled. These results strengthen the argument for the potential application of Mycobacterium sp. PYR‐1 for bioremediation of PAH‐contaminated wastes.     

Heritability of Morningness‐Eveningness and Self‐Report Sleep Measures in a Family‐Based Sample of 521 Hutterites

Individual variation in the phase and amplitude of human circadian rhythms is well known, but the impact of heritable factors on such variation is less clear. We estimated the narrow‐sense heritability for selected circadian and sleep timing, quality, and duration measures among related members of the Hutterites, an endogamous, religious community (n=521 participants). “Morningness‐eveningness” (M/E), a stable trait reflecting circadian phase, was evaluated using the Composite Scale (CS). Subjective sleep measures were assessed using the Sleep Timing Questionnaire. Initial analyses reconfirmed the impact of age on M/E. Previously reported correlations between M/E scores and the sleep measures were also noted, demonstrating the construct validity of the questionnaires among the participants. Following corrections for age, gender, and colony of residence, significant narrow‐sense heritability was noted for M/E (23%). The heritability for subjective sleep measures (related to timing, duration, and quality) were statistically significant for all but one variable, and varied between 12.4% and 29.4%. Thus, significant heritable influences on human circadian phase and subjective sleep indices can be detected through family‐based studies. In view of the impact of circadian malfunction on human health, it may be worthwhile to map genetic factors impacting circadian and sleep variation.     

Effect of Time‐of‐Day‐Specific Strength Training on Serum Hormone Concentrations and Isometric Strength in Men

A time‐of‐day influence on the neuromuscular response to strength training has been previously reported. However, no scientific study has examined the influence of the time of day when strength training is performed on hormonal adaptations. Therefore, the primary purpose of this study was to examine the effects of time‐of‐day‐specific strength training on resting serum concentrations and diurnal patterns of testosterone (T) and cortisol (CORT) as well as maximum isometric strength of knee extensors. Thirty eight diurnally active healthy, previously untrained men (age 20–45 yrs) underwent a ten‐week preparatory strength training period when sessions were conducted between 17:00–19:00 h. Thereafter, these subjects were randomized into either a morning (n=20, training times 07:00–09:00 h) or afternoon (n=18, 7:00–19:00 h) training group for another ten‐week period of time‐of‐day‐specific training (TST). Isometric unilateral knee extension peak torque (MVC) was measured at 07:00, 12:00, 17:00, and 20:30 h over two consecutive days (Day 1 & Day 2) before and after TST. Blood samples were obtained before each clock‐time measurement to assess resting serum T and CORT concentrations. A matched control group (n=11) did not train but participated in the tests. Serum T and CORT concentrations significantly declined from 07:00 to 20:30 h on all test days (Time effect, p<.001). Serum CORT at 07:00 h was significantly higher on Day 1 than Day 2 in the control and afternoon group, both in Pre and Post conditions (Day×Time interaction, p<.01). In the morning group, a similar day‐to‐day difference was present in the Pre but not Post conditions (Time×Group interaction, p<.05). MVC significantly increased after TST in both the morning and afternoon groups (Pre to Post effect, p<.001). In both groups, a typical diurnal variation in MVC (Time effect, p<.001) was found, especially on Day 2 in the Pre condition, and this feature persisted from Pre to Post in the afternoon group. In the morning group, however, diurnal variation was reduced after TST on both Day 1 and Day 2 (Pre to Post×Day×Time×Group interaction, p<.05). In conclusion, 10 weeks of morning time‐of‐day‐specific strength training resulted in reduced morning resting CORT concentrations, presumably as a result of decreased masking effects of anticipatory psychological stress prior to the morning testing. The typical diurnal pattern of maximum isometric strength was blunted by the TST period in the morning but not the afternoon group. However, the TST period had no significant effect on the resting total T concentration and its diurnal pattern and on the absolute increase in maximum strength.     

Combinations of 5‐Fluorouracil with UCN‐01 or Staurosporine

The action of 5‐Fluorouracil (5‐FU) is mediated by inhibition of thymidylate synthase (TS), which is regulated by cell cycle proteins controlled by protein phosphorylation. We studied the effects of staurosporine and its analogue UCN‐01, inhibitors of protein kinase C (PKC) on 5‐FU cytotoxicity in Lovo colon cancer cells. Each drug contributes equally to the cell cycle effects of the 5‐FU combinations. In sequential drug administration, the cell cycle distribution was determined by the first drug. Simultaneous 5‐FU combinations induced additive effects in induction of apoptosis. When staurosporine was used as the second drug, induction of apoptosis was 2‐fold higher than the sum of both drugs alone. Based on induction of apoptosis 5‐FU addition prior to the PKC inhibitors seemed preferable.     

Historian‐judges of Korean nationalism

Studies of Korean nationalism have not only been less researched but they have also been predominantly nationalistic and moralistic. Authors have tended to assume an already present nationalism ever since the late‐nineteenth century. They have omitted analysis of the mechanism of the emergence of Korean nationalism and so have merely substantiated the concept. This tendency is attributed both to the lack of methodological sophistication ‐ most of them apply the concept of nationalism teleologically and without theoretical rigour ‐ and also to the ideology of the authors themselves. The aim of this article is to expose some of the current problems recognized in this area through the examination of works by selected authors.     

Genetic regulation of self‐incompatibility

Self‐incompatibility is a cell‐cell recognition system in higher plants that is based on the ability of the pistil to discriminate “self‐pollen from “non‐self"‐pollen. In the simplest systems, this recognition response is controlled by a single locus — the S‐locus — with multiple alleles. Pollination of a pistil with pollen bearing an S‐allele recognition factor identical to that expressed in the host plant stigma or style results in rejection of the “self"‐pollen. Most of the studies on the molecular genetics of self‐incompatibility that are summarized in this review have had as their goal the identification and characterization of the gene product(s) associated with the self‐incompatibility response. These studies have provided a great deal of new and important information about self‐incompatibility — despite the fact that many critical questions remain unresolved. Taken together, the present evidence from these studies indicates that the self‐incompatibility response is likely to be far more complex than suggested by historical models.     

Synthesis of Oligoribonucleotides Containing 4‐Thiouridine Using the Convertible Nucleoside Approach and the 1‐(2‐Fluorophenyl)‐4‐Methoxypiperidin‐4‐yl Group

Oligoribonucleotides containing 4‐thiouridine were prepared using the Fpmp group for protection of the 2′‐OH. Two uridine derivatives with the 1,2,4‐triazolyl and the 2‐nitrophenyl groups at position 4 were used to obtain 4‐thiouridine by postsynthetic substitution with sodium hydrogen sulfide. Both uridine derivatives allow the preparation of the desired oligonucleotides in good yields.     

Second Generation of cycloSal‐Pronucleotides with Esterase‐Cleavable Sites: The ”Lock‐In”‐Concept

A conceptual extension of the cycloSal‐pronucleotide approach is presented. The characteristic feature of the new cycloSal‐derivatives of the anti‐HIV active nucleoside analogue d4T 1 is the incorporation of an enzymatically cleavable carboxylic ester moiety with the intention to trap the triesters inside cells (”lock‐in”‐concept). CycloSal‐triesters bearing different ester groups in the 3‐or 5‐position of the cycloSal‐moiety are described. Surprisingly, only acetyl‐and levulinyl esters are cleaved readily in CEM cell extracts while alkyl esters were found to be stable. Nevertheless, in in‐vitro anti‐HIV assays most of the compounds achieve the thymidine–kinase bypass, thus proving that they act at least as nucleotide delivery systems.     

Plants‐associated microflora and the remediation of oil‐contaminated soil

The use of plants and their rhizospheric microorganisms is a promising emerging technology for remediating contaminated soils. The degradation of total petroleum hydrocarbon (TPH) in the rhizospheric and nonrhizospheric soil of three domestic plants, namely, alfalfa (Medicaga sativa) broad beans (Vicia faba) and ryegrass (Lolium perenne) was investigated. The experimental data from the studies of plantmicrobe‐soil interactions implicated the enhancement of TPH degradation by the rhizospheric microbial community. Although the three domestic plants exhibited normal growth in the presence of ～1.0% TPH, the degradation was more profound in the case of leguminous plants. The TPH degradation in the soil cultivated with broad beans and alfalfa was 36.6 and 35.8%, respectively, compared with 24% degradation in case of ryegrass. Such a high correlation between plant type and TPH degradation rates indicate that selection for enhanced rhizosphere degradation may be accomplished by selecting leguminous plants.