ALBERT

Notes: Summary 1. In populations of the dipteran Phryne cincta (2n = 6+XX♀, XY♂) several X-chromosomes of different structure are present. These are allocyclic in contrast to the (eucyclic) autosomes, as seen in their behaviour in mitosis and meiosis and in their varied appearance in polytene nuclei (comp. Wolf 1950, 1957). 2. The polytene autosomes (2–4 s. Pig. 7) differ from each other in easily recognizable characters and form no chromocenter. The polytene X-chromosome is always relatively much shorter than the autosomes and more or less β-heterochromatic (granular or indistinctly banded) in larvae, raised at room temperature. In larvae raised at low temperature (0–4° C) it passes through a morphogenesis, growing to normal or nearly normal length and assuming the aspect of an euchromatic element (comp. X a in Figs. 3 and 4). 3. Two stocks, characterized by different X-chromosomes, symbolized by X a and X b or a and b respectively, were chosen for the experiments. In mitosis both these X-chromosomes are rod-like, a is as long as autosome 4, b has only half its length (Figs. 1, 2a–d). 4. Just before pupation, in polytene nuclei of larvae raised at low temperature a and b are of almost equal length. They differ from each other in several inversions and in the appearance of two large α-heterochromatic bands in a (α2 and α3, Fig. 5; “α-quantum-difference”). 5. The α-bands, especially the large block α2, show a considerable intercellular variation in their relative DNA-content (measured as length of the α-element). The mean DNA-content is negatively correlated with the degree of stretching of the chromosome (Table 1). 6. In polytene nuclei of female hybrids from the crosses aaxbY or bbxaY, a and b are unpaired or incompletely paired in variable degrees (Figs. 7, 8a–e). The heterozygotic chromosome pair can be devided into 5 segments (I–V, Fig. 6), three of which are marked by clearly defined structural differences (I, III, V). 7. The pairing-segments II and IV, exhibiting an identical and parallel sequence of discs in a and b, allow six crossing-over recombinations (cb, db, eb, fb, gb, hb; comp. Figs. 9, 10). These new types of X-chromosomes occur in very different frequencies in the progeny of the hybrid ♀♀ when backcrossed to standard ♂♂ bY. The types eb and fb occur relatively rarely, while gb and hb are extremely rare (Figs. 9, 10, Table 2); in 70% of the progenies they are not present. The recombination-process is mainly restricted to pairing segment IV. 8. In a and in the crossover-chromosomes c, e, g very often a threadlike constriction appears in the region of α 2, resulting mostly in a pseudofragmentation with more or less independent location of the two chromosome parts (Figs. 3d, 8f-i, 11a). A variety of kinds of fusion between the parts and the autosomes, especially in their α-heterochromatin, is possible (Figs. 3e, 8g–i). 9. Lowering the breeding-temperature increases the duration of development, the size of the larvae, and the lengthening and euchromatization of the β-heterochromatic parts of the X-chromosomes. In the hybrids it also results in increasing the recombination rate (Table 3 and 4). 10. In the main experiments, hybrid offspring from the same parental pair, were raised at different temperatures: some individuals at high (20–26° C), others at low temperatures (2–8° C). The resulting two series of imagos were kept in optimal or room temperatures (14–22° C). The female progeny of 23 hybrids raised at elevated temperature and of 27 hybrids raised at low temperature, i.e. 1766 and 2102 X-chromosomes respectively, have been tested (Table 5, Fig. 12). No or only little recombination occurred in hybrids raised at 20–26° C (mean = 2.4%) in contrast to their sisters raised at 2–8° C, which gave a relative high frequency (mean = 18,2%). 11. In these cases only the first egg batches of each hybrid ♀ have been evaluated. Later progeny exhibits a reduction in crossing-over frequency in cold-raised hybrids with growing age. The mean rate of recombination of 14 hybrids is lowered from 16,6% in the first to 7,1% in the following progeny (n=1813; Table 6, Fig. 15) presumably as a consequence of keeping the imago in higher temperature. 12. The results from several larger groups of cold-raised sister hybrids more or less clearly demonstrate a bimodal distribution of recombination values (Fig. 13) suggesting a difference in recombination potentiality between the two X-chromosomes in the mother of the hybrids. Some data indicate the recombination rate in the X-chromosome as negatively correlated with the rate of development (Table 7). 13. The Mendelian ratio, 1∶1, of the non-recombinant types, ab and bb, is found in the progeny of the warm-raised hybrids (1769∶1778). This ratio is shifted considerably in favour of type ab in the case of low temperature hybrids (1996∶1626). In the recombinant types, cb and db, the ratio is always markedly shifted in favour of cb, irrespective of temperature (712:343). There must exist a causal relation between the Mendelian anomaly and the recombination process the nature of which is yet unknown. 14. The temperature at which a larva is raised effects both the frequency of crossing over and the stretching and euchromatization of β-heterochromatin in the polytene X-chromosome. This parallele suggests that structural changes comparable to those in the polytene chromosomes are induced by low temperature in meiotic chromosomes as well, and that these changes are responsible for the effect on the crossing-over frequency. These changes, which are reversible by age or temperature, are supposed to cause the extention of the “effective pairing” (as in euchromatic segments) on β-heterochromatic elements, which normally are unpaired. 15. The so-called “α-quantum-difference”, i.e. the difference in the amount of α-heterochromatin (or in the “relative DNA-content”) between the X-chromosomes is considered to be causally related to the crossing-over process (“α-differential-effect”). By way of a potential function it effects crossing over not only within the “α-differential” tetrad but also crossing over in non-homologous and unrelated pairs of chromosomes in the same meiotic cell. 16. This hypothesis was ascertained by two independent inversions in autosome 2 (In 2a and In 2b, Fig. 16) which permitted to test the influence of the “α-quantum-difference” in the X-chromosomes on crossing over in the autosome. In preliminary studies the progenies of 8 females (ab, bb, cb) and 3 males (aY, cY) of the heterozygous F1 backcrossed to homozygous b-stock have been investigated. In the progeny of the males only the parental combinations in autosome 2 were found. In the test cross progeny of the females the two expected types of recombination appeared (with only one inversion, In 2a or In 2b), but there existed a very high difference in linkage between bb- ♀♀ on the one side (3.6% crossing over) and ba- and bc-♀♀ on the other (40.2% crossing over).

Notes: Summary A system for monitoring adverse drug reactions (ADR) in psychiatric inpatients was introduced in psychiatric hospitals in the FRG in May 1979. It consists of intensive drug monitoring (IDM) and a so-called “organized spontaneous reporting system” (OSR). ADR are rated separately according to impact on therapy and probability of causal relationship. With IDM all ADR (Grades I–III) are assessed in a randomly selected sample of inpatients. With OSR only ADR leading to discontinuation of the drugs in question (=ADR Grade III) are assessed. In 406 drug-treated inpatients monitored by IDM in the psychiatric hospitals of Berlin and Munich from May 1979 to Dec. 1981, ADR were observed in 60,4%. In 15% of IDM-patients ADR led to discontinuation of the drugs in question; with OSR the relative frequency of these Grade III ADR was 9,0% in 5096 patients monitored throughout the entire period. Life-threatening events were observed in 1,2% of patients undergoing IDM as well as 1.2% of those undergoing OSR. The most frequently observed ADR by IDM were sedation, extrapyramidal signs, disturbances of the autonomic nervous system and increase in transaminases, and by OSR Parkinsonism, akathisia, sedation, toxic delirium and increased transaminases. The relative frequency of Grade III ADR was similar for neuroleptics and antidepressants (5,4% and 5,3% in OSR); a very low relative frequency of ADR Grade III was found for tranquilizers and hypnotics (0,7% and 0,2%). Methodological aspects of this drug monitoring system are discussed in the light of current literature.

Notes: Zusammenfassung Die bei der Polymerisation von Styrol in n-Heptanlösung bei Anregung mit n-Butyllithium entstehenden Polymeren bestehen aus einem verhältnismäßig eng verteilten kurzkettigen Anteil und einem längerkettigen mit breiterer Verteilung. Das kristallisationsfähige Polymere ist im langkettigen Anteil enthalten. Unter den Bedingungen, unter welchen neben dem ataktischen Polymeren auch isotaktisches entsteht, ist die Zahl der gebildeten Polymermolekeln bedeutend geringer als diejenige der im System vorhandenen n-Butyllithiummolekeln.

Notes: Zusammenfassung Die Molekulargewichtsverteilung von Polystyrolen, die mit Radikalstartern unter besonderen Vorsichtsmaßnahmen hergestellt worden waren, wurde nochmals kritisch im Hinblick auf die Beteiligung der Disproportionierung am gesamten bimolekularen Abbruch untersucht. Dabei wurde auch der Einfluß des Primärradikalabbruchs und der Monomerübertragung auf die Molekulargewichtsverteilung quantitativ erfaßt. Der experimentell durch Säulenfraktionierung festgestellte Anteil an Polymerem vom Kopplungsgrad Eins ist jedoch deutlich größer, als durch Monomerübertragung und durch Primärradikalabbruch erklärt werden kann; für den Differenzbetrag kommt nur eine neben der Kombination zweier Radikalketten verlaufende Disproportionierung in Frage, deren Anteil am gesamten bimolekularen Abbruch zwischen zwei Radikalketten im Temperaturbereich von 20–50°C etwa 17% beträgt.

Notes: Summary From the break-down in the viscosity of a polymer solution, associated with the entrance into the two phase region, the pressure dependence of the demixing temperatures of solutions of polystyrene (M = 600.000) in cyclohexane, cyclopentane, diethylmalonate and 1-phenyldecane was measured up to 1000 bar. The application of pressure increases the solubility of polystyrene in cyclopentane and diethylmalonate, but decreases that in 1-phenyldecane; in the case of cyclohexane, a pressure of optimum miscibility is observed at ca. 120 bar. The discussion of these findings, together with further information from the literature, demonstrates that current theories cannot even predict the pressure influences qualitatively. For an easy forecast of the effects, the distance of the (upper) critical solution temperature,T c from the melting point of the solvent,T MP, can, however, serve as a guideline: From the present material it can be concluded thatT c is increased by pressure if (T —T MP)/T MP (K/K) is less than 0,20 but decreased it if it exceeds 0,25.

Notes: Solutions of poly (decyl methacrylate) in isooctane (2,2, 4-trimethylpentane) show lower critical solution temperatures (LCST) that lie well below the thermal degradation of the polymer. The corresponding exothermal theta-temperature (from the Shultz-Flory plot) amounts to 210°C. The increase in solvent quality by pressure turns out to be very pronounced (d Tc/dp ≈ +1 K/bar). With solutions of the polymer in motor oils, high temperature demixing is unlikely to occur below their boiling point. The theoretical evaluation of published experimental data for 11 different systems exhibiting LCSTs demonstrates the following: Under the equilibrium vapour pressure of the solution high temperature demixing is generally observed withing the temperature interval between Tb, the boiling point of the pure solvent (1 bar), and 1,5 Tb. As Tc - Tb increases, the heats of mixing and the pressure influence on Tc increase, too.

Notes: The viscosity of solutions of poly(decyl methacrylate)s, PDMA, in 1-pentanol (thermodynamically poor solvent) and in toluence or isooctane (good solvents) was measured up to shear rates of 3 · 104s-1 by means of rotational viscosimeters. The observed pronounced shear thinning is for all solutions well described by the theory of Graessley, with the extension, introduced by Ito. Two parameters, resulting from the evaluation of the flow curves on the basis of the above theory, are discussed: τ0, a characteristic relaxation time of the polymer chain, is found to be in the range of ms. ηfric, a frictional parameter, independent of shear rate, amounts upto 50% of the zero-shear viscosity for the measured solutions. Both, τ0 and ηfric, increase with decreasing solvent quality, increasing molecular weight, and increasing concentration, in accord with theory. A comparatively sharp downward bend, separating two power-law regimes, shows up with moderately concentrated solutions, as the shear rate exceeds about 103 to 104 s-1. This transition is tentatively interpreted as an orientation of the long side chains of PDMA.

Notes: By means of data from critical demixing and vapour pressure measurements and by inverse gas chromatography, including the results of published light scattering measurments, a consistent picture is obtained for the entire dependence of the Flory-Huggins parameter χ on the weight fraction w2 of the polymer and on the temperature T for the system tert-butyl acetate/polystyrene. Within the entire T-range (ca. 0°C - 140°C), χ increases stronger than exponentially with w2, the rise being the larger the larger χH (the enthalpy contribution to χ) becomes in the limit of infinite dilution. At sufficiently high temperatures (≳ 50°C), χH changes its sign from negative to positive as w2 is raised. This behaviour, as well as the general shape of χ(w2) is in qualitative accord with the results of the corresponding-states theory as developed by Flory et al.

Notes: In order to investigate the influences of different end-groups on oligomer miscibility with other substances, oligo(propylene glycol)s bearing —OH groups (OPG-OH) studied in the previous paper2, were acetylated at both ends (OPG-AC). The limits of miscibility of OPG-AC with oligo(dimethylsiloxane) (ODMS) were measured turbidimetrically. A simple and reliable method for the determination of the critical points from turbidity data is presented. The observed upper critical temperatures (Tc) increase with degree of oligomerization of ODMS (ranging from 1 to 5), whereas Tc shows a minimum when the degree of oligomerization of the OPG-AC is raised (from 1 to 57,5). For lower mol. wt. oligoglycols, the Tc-values of ODMS/OPG-AC are lower by ca. 50 K as compared with those of ODMS/OPG-OH. The different end-groups play a minor role with respect to the pressure influences (up to 1 500 bar the miscibility increases in all cases). For OPG-AC the chain length of optimum miscibility with a given ODMS is found at considerably lower values than for OPG-OH. The theoretical evaluation of the experimental material on the basis of the lattice theory yields a reduction in the enthalpies of mixing up to 10% and an increase in the volumes of mixing (〈0) up to 50% when —OH is replaced by —AC. For the treatment of end-group effects, the solubility parameter theory, when combined with the concept of molar attraction constants, presents several advantages: In particular it is possible to describe the phase separation behaviour of the different oligomer mixtures simply by means of solubility parameters and molar volumes of the different segments and end-groups and to forecast the presence or absence of a chain-length of optimum miscibility.

Notes: An apparatus is presented for the precise measurement of vapour pressures. It is tested with diethyl ether and applied to the system tert-butyle acetate/polystyrene (weight-average molecular weight Mw = 110000) up to polymer concentrations of ca. 60 wt.-% in the temperature range from 10 to 90°C; by means of the Redlich-Kister equation the results can well be described analytically. The data are evaluated to yield the Flory-Huggins parameter in the subsequent article in conjunction with other experimental information.