Optimal simultaneous maximum a posterioriestimation of states, noise statistics and parameters I. Algorithm

The simultaneous state and parameter estimation problem for a linear discrete-time system with unknown noise statistics is treated as a large-scale optimization problem. The a posterioriprobability density function is maximized directly with respect to the states and parameters subject to the constraint of the system dynamics. The resulting optimization problem is too large for any of the standard non-linear programming techniques and hence an hierarchical optimization approach is proposed. It turns out that the states can be computed at the first levelfor given noise and system parameters. These, in turn, are to be modified at the second level.The states are to be computed from a large system of linear equations and two solution methods are considered for solving these equations, limiting the horizon to a suitable length. The resulting algorithm is a filter-smoother, suitable for off-line as well as on-line state estimation for given noise and system parameters. The second level problem is split up into two, one for modifying the noise statistics and the other for modifying the system parameters. An adaptive relaxation technique is proposed for modifying the noise statistics and a modified Gauss-Newton technique is used to adjust the system parameters.

The Crystal Structure of Pivaloyl- D- prolyl-L- prolyl- L-alanyl-N- methylamide

Pivaloyl-D-prolyl-L-prolyl-L-analyl-N-methylam~de (I), C1UH32N40c4r,y stallizes in the orthorhombic space group P21212,w ith four molecules in a unit cell of dimensions a = 9.982 (l),b = 10.183 (3), c = 20.746 (2)A . The structure has been refined to R 0.048 for 1 745 observed reflections. All the peptide bonds in the molecule are trans and both the prolyl residues are in the CY-exo-conformation. The molecule assumes a highly folded conformation in which a Type II' DL bend is followed by a Type I LL bend, both stabilised by intramolecular 4 + 1 hydrogen bonds. This conformation, which has been observed for the first time, is of interest in relation to the structure of gramicidin S.

Studies on follicular atresia: role of tropic hormone and steroids in regulating cathepsin-D activity of preantral follicles of the immature rat

The ovary of the immature female rat is comprised of primary and medium-sized preantral follicles. Upon stimulation with FSH or PMSG, the cathepsin-D activity, a representative lysosomal enzyme of granulosa cells, is reduced by 50% (P < 0.01). 17β-Estradiol at the doses tried was unable to mimic this effect. Blockade of steroidogenesis with cyanoketone also had no effect on the cathepsin-D activity of isolated granulosa cells. Dihydrotestosterone (DHT), however, at a dose of 1 mg/rat was able to inhibit PMSG's tropic action. It brought about an increase in cathepsin-D activity and reduction in steroidogenic activity of isolated granulosa cells. The atretogenic activity of DHT could be relieved by supplementation with exogenous FSH. DHT was observed to significantly reduce (P < 0.01) endogenous FSH and LH levels within 12–18 h of its injection suggesting that its atretic effect was due to its action at the pituitary rather than the gonad. In addition to the above the ability of 15 IU of PMSG to reduce cathepsin-D activity of granulosa cells was also significantly reduced (P < 0.01) if endogenous FSH was neutralized by a specific FSH antiserum. The present study suggests that as far as small and medium-sized primary and preantral follicles are concerned, FSH lack is the essential signal for onset of atresia.

Structural analyses of (1->3),(1->4)-β-D-glucan of oats and barley

The structures of (1→3),(1→4)-β-D-glucans of oat bran, whole-grain oats and barley and processed foods were analysed. Various methods of hydrolysis of β-glucan, the content of insoluble fibre of whole grains of oats and barley and the solution behaviour of oat and barley β-glucans were studied. The isolated soluble β-glucans of oat bran and whole-grain oats and barley were hydrolysed with lichenase, an enzyme specific for (1→3),(1→4)-β-D-β-glucans. The amounts of oligosaccharides produced from bran were analysed with capillary electrophoresis and those from whole-grains with high-performance anion-exchange chromatography with pulse-amperometric detection. The main products were 3-O-β-cellobiosyl-D-glucose and 3-O-β-cellotriosyl-D-glucose, the oligosaccharides which have a degree of polymerisation denoted by DP3 and DP4. Small differences were detected between soluble and insoluble β-glucans and also between β-glucans of oats and barley. These differences can only be seen in the DP3:DP4 ratio which was higher for barley than for oat and also higher for insoluble than for soluble β-glucan. A greater proportion of barley β-glucan remained insoluble than of oat β-glucan. The molar masses of soluble β-glucans of oats and barley were the same as were those of insoluble β-glucans of oats and barley. To analyse the effects of cooking, baking, fermentation and drying, β-glucan was isolated from porridge, bread and fermentate and also from their starting materials. More β-glucan was released after cooking and less after baking. Drying decreased the extractability for bread and fermentate but increased it for porridge. Different hydrolysis methods of β-glucan were compared. Acid hydrolysis and the modified AOAC method gave similar results. The results of hydrolysis with lichenase gave higher recoveries than the other two. The combination of lichenase hydrolysis and high-performance anion-exchange chromatography with pulse-amperometric detection was found best for the analysis of β-glucan content. The content of insoluble fibre was higher for barley than for oats and the amount of β-glucan in the insoluble fibre fraction was higher for oats than for barley. The flow properties of both water and aqueous cuoxam solutions of oat and barley β-glucans were studied. Shear thinning was stronger for the water solutions of oat β-glucan than for barley β-glucan. In aqueous cuoxam shear thinning was not observed at the same concentration as in water but only with high concentration solutions. Then the viscosity of barley β-glucan was slightly higher than that of oat β-glucan. The oscillatory measurements showed that the crossover point of the G´ and G´´ curves was much lower for barley β-glucan than for oat β-glucan indicating a higher tendency towards solid-like behaviour for barley β-glucan than for oat β-glucan.

Cord blood 25-hydroxyvitamin D and fetal growth in the China-Anhui birth cohort study

We determined the association of cord blood 25-hydroxyvitamin D [25(OH)D] with birth weight and the risk of small for gestational age (SGA). As part of the China-Anhui Birth Cohort (C-ABC) study, we measured cord blood levels of 25(OH)D in 1491 neonates in Hefei, China. The data on maternal sociodemographic characteristics, health status, lifestyle, birth outcomes were prospectively collected. Multiple regression models were used to estimate the association of 25(OH)D levels with birth weight and the risk of SGA. Compared with neonates in the lowest decile of cord blood 25(OH)D levels, neonates in four deciles (the fourth, fifth, sixth and seventh deciles) had significantly increased birth weight and decreased risk of SGA. Multiple linear regression models showed that per 10 nmol/L increase in cord blood 25(OH)D, birth weight increased by 61.0 g (95% CI: 31.9, 89.9) at concentrations less than 40 nmol/L, and then decreased by 68.5 g (95% CI: −110.5, −26.6) at concentrations from 40 to 70 nmol/L. This study provides the first epidemiological evidence that there was an inverted U shaped relationship between neonatal vitamin D status and fetal growth, and the risk of SGA reduced at moderate concentration.

Identification of intersectional Corymbia hybrids based on seedling morphology improves with parental divergence

Differences in morphology have provided a basis for detecting natural interspecific hybridisation in forest trees for decades but have come to prominence again more recently as a means for directly measuring gene flow from planted forests. Here we examined the utility of seedling morphology for hybrid discrimination in three hybrid groups relevant to the monitoring of gene flow from plantings of Corymbia (L.D. Pryor & L.A.S. Johnson ex Brooker) taxa in subtropical Australia. Thirty leaf and stem characters were assessed on 907 8-month old seedlings from four parental and six hybrid taxa grown in a common garden. Outbred F1 hybrids between spotted gums (Corymbia citriodora subspecies variegata, C. citriodora subspecies citriodora and Corymbia henryi) tended to more closely resemble their maternal Corymbia torelliana parent and the most discriminating characters were the ratio of blade length to maximum perpendicular width, the presence or absence of a lignotuber, and specific leaf weight. Assignment of individuals into genealogical classes based on a multivariate model limited to a set of the more discriminating and independent characters was highest in the hybrid group, where parental taxa were genetically most divergent. Overall power to resolve among outbred F1 hybrids from both parental taxa was low to moderate, but this may not be a limitation to its likely major application of identifying hybrids in seedlots from native spotted gum stands. Advanced generation hybrids (outbred F2 and outbred backcrosses) were more difficult to resolve reliably due to the higher variances of hybrid taxa and the tendency of backcrosses to resemble their recurrent parents. Visual assessments of seedling morphology may provide a filter allowing screening of the large numbers needed to monitor gene flow, but will need to be combined with other hybrid detection methods to ensure hybrids are detected.

Jewish cemetery; Gemuenden a.d. Wohra Cemeteries

Digital Image

Defining Adequate Vitamin D Intake : Cross-sectional and Intervention Studies

D-vitamiini ylläpitää normaalia luun kasvua ja uudistumista koko elämän ajan. Suomessa, kuten monissa muissakin länsimaissa, väestön D-vitamiinitilanne on riittämätön – talvisin osalla jopa puutteellinen. Tässä väitöskirjassa on tutkittu, lisääkö D-vitamiini luumassan kertymistä kasvuiässä, ja ylläpitäkö D-vitamiini luuston tasapainoista aineenvaihduntaa aikuisiällä. Nämä vaikutukset saattavat ehkäisi osteoporoosin kehittymistä eri ikäkausina. Väitöskirjatyössä tutkittiin erisuuruisten D-vitamiinilisäysten vaikutuksia kolmessa eri ikäryhmässä, jotka olivat 11-12 -vuotiaat tytöt (N=228), 21-49 -vuotiaat miehet (N=54) ja 65-85 -vuotiaat naiset (N=52). Tutkittavat satunnaistettiin ryhmiin, jotka nauttivat joko lumevalmistetta tai 5-20 µg D3-vitamiinia vitamiinilisänä. Tutkimukset olivat kaksoissokkoutettuja. Tutkimuksen aikana tutkittavilta otettiin paastoveri- ja virtsanäytteitä. Lisäksi he täyttivät tutkimuslomakkeen taustatietojen kartoittamiseksi sekä frekvenssikyselylomakkeen kalsiumin ja D-vitamiinin saannin selvittämiseksi. Tyttöjen luunmineraalitiheys (BMD) mitattiin DXA–laitteella ja miesten volumetrinen luuntiheys pQCT-menetelmällä. Näytteistä määritettiin mm. seerumin 25-hydroksi-D-vitamiinin (=S-25-OHD), lisäkilpirauhashormonin (=S-PTH) ja luun aineenvaihduntaa kuvaavien merkkiaineiden pitoisuuksia. Murrosikäisten tyttöjen poikkileikkaustutkimuksessa S-25-OHD- ja luun muodostusmerkkiaineen pitoisuudet vaihtelivat kuukausien välillä; suurimmat pitoisuudet mitattiin syyskuussa ja pienimmät maaliskuussa, mikä kuvastaa vuodenaikaisvaihtelua. Vastaava vaihtelu havaittiin lannerangan ja reisiluun BMD:ssä. D-vitamiinilisäyksellä oli myönteinen vaikutus tyttöjen luumassan lisääntymiseen. Suurin D-vitamiinilisä (10 µg/vrk) lisäsi luumassaa 17.2% enemmän reisiluussa ja 12.5% enemmän lannerangassa verrattuna lumevalmistetta nauttivien tyttöjen vastaaviin tuloksiin, mutta tulos riippui hoitomyöntyvyydestä. D-vitamiinin vaikutus luustoon välittyi vähentyneen luun hajotuksen kautta. Tutkimustuloksiin perustuen riittävä D-vitamiinin saanti murrosikäisille tytöille on 15 µg/vrk. D-vitamiinilisän vaikutus 65-85 -vuotiaiden naisten S-25-OHD-pitoisuuteen vakioitui kuudessa viikossa annoksen ollessa 5-20 µg/vrk. Näillä D-vitamiiniannoksilla ei saavutettu tavoiteltavaa S-25-OHD-pitoisuutta, joka on 80 nmol/l. Arvioimme, että 60 nmol/l -pitoisuuden, jota esiintyy kesäisin tämän ikäryhmän suomalaisilla, tämän ikäryhmän naiset saavuttaisivat 24 µg:n päivittäisellä D-vitamiinin saannilla. Terveillä miehillä havaittiin vuodenaikaisvaihtelu S-25-OHD- ja S-PTH-pitoisuudessa sekä luun hajotusta kuvaavassa merkkiainepitoisuudessa. Toisaalta vaihtelua ei havaittu radiuksen volumetrisessä luuntiheydessä eikä luun muodostusmerkkiaineen pitoisuudessa. Vuodenaikaisvaihtelu estettiin 17 µg:n päivittäisellä D-vitamiinin saannilla, mutta tämän ei havaittu vaikuttavan radiuksen luuntiheyteen kuusi kuukautta kestävän tutkimuksen aikana. Yhteenvetona todetaan, että D-vitamiinin saanti on edelleenkin riittämätöntä tutkimusten kohderyhmillä. Tämä näkyy S-25-OHD- ja PTH-pitoisuuden sekä luunaineenvaihduntaa kuvaavien merkkiaineiden vuodenaikaisvaihteluna, mikä on haitallista luuston hyvinvoinnille. D-vitamiinin saantia tulisi lisätä, jotta vähintäänkin riittävä D-vitamiinitilanne (S-25-OHD>50 nmol/l) tai mahdollisesti jopa tavoiteltava D-vitaminitilanne (S-25-OHD≥80 nmol/l) saavutettaisiin. Jotta D-vitamiinin saannin lisääminen olisi kaikissa ikäryhmissä mahdollista, on suunniteltava nykyistä enemmän D-vitamiinilla täydennettyjä elintarvikkeita.

Improved optical character recognition by matched filtering

The effectiveness of linear matched filters for improved character discrimination in presence of random noise and poorly defined characters has been investigated. We have found that although the performance of the filter in presence of random noise is reasonably good (16 dB gain in signal-to-noise-ratio) its performance is poor when the unknown character is distorted (linear shift and rotation).

Sitting l-r Rabbi Dudley Weinberg, Leo Baeck, Joseph H. Cohen, Dr. Joshua Liebman; Standing l-r Max Feldberg, Louis Salvage, Rabbi Beryl D. Cohon, Harry Penn, Abraham Schiller; Boston Portraits; Groups; Men

Page 58 of the "American Jewish Cavalcade" scrapbook of Leo Baeck in New York found in ROS 10 Folder 3

A rational approach to the synthesis of one-dimensional acoustic filters

The velocity ratio algorithm developed from a heuristic study of transfer matrix multiplication has been employed to bring out the relative effects of the elements constituting a linear, one-dimensional acoustic filter, the overall dimensions of which are fixed, and synthesize a suitable straight-through configuration for a low-pass, wide-band, non-dissipative acoustic filter. The potential of the foregoing approach in applications to the rational design of practical acoustic filters such as automotive mufflers is indicated.

Synthesis, Reactivity and Biological Activity of 17β-HSD1 Inhibitors Based on a Thieno[2,3-d]pryrimidin-4(3H)-one Core

Breast cancer is the most common cancer in women in Western countries. In the early stages of development most breast cancers are hormone-dependent, and estrogens, especially estradiol, have a pivotal role in their development and progression. One approach to the treatment of hormone-dependent breast cancers is to block the formation of the active estrogens by inhibiting the action of the steroid metabolising enzymes. 17beta-Hydroxysteroid dehydrogenase type 1 (17beta-HSD1) is a key enzyme in the biosynthesis of estradiol, the most potent female sex hormone. The 17beta-HSD1 enzyme catalyses the final step and converts estrone into the biologically active estradiol. Blocking 17beta-HSD1 activity with a specific enzyme inhibitor could provide a means to reduce circulating and tumour estradiol levels and thus promote tumour regression. In recent years 17beta-HSD1 has been recognised as an important drug target. Some inhibitors of 17beta-HSD1 have been reported, however, there are no inhibitors on the market nor have clinical trials been announced. The majority of known 17beta-HSD1 inhibitors are based on steroidal structures, while relatively little has been reported on non-steroidal inhibitors. As compared with 17beta-HSD1 inhibitors based on steroidal structures, non-steroidal compounds could have advantages of synthetic accessibility, drug-likeness, selectivity and non-estrogenicity. This study describes the synthesis of large group of novel 17beta-HSD1 inhibitors based on a non-steroidal thieno[2,3-d]pyrimidin-4(3H)-one core. An efficient synthesis route was developed for the lead compound and subsequently employed in the synthesis of thieno[2,3-d]pyrimidin-4(3H)-one based molecule library. The biological activities and binding of these inhibitors to 17beta-HSD1 and, finally, the quantitative structure activity relationship (QSAR) model are also reported. In this study, several potent and selective 17beta-HSD1 inhibitors without estrogenic activity were identified. This establishment of a novel class of inhibitors is a progressive achievement in 17beta-HSD1 inhibitor development. Furthermore, the 3D-QSAR model, constructed on the basis of this study, offers a powerful tool for future 17beta-HSD1 inhibitor development. As part of the fundamental science underpinning this research, the chemical reactivity of fused (di)cycloalkeno thieno[2,3-d]pyrimidin-4(3H)-ones with electrophilic reagents, i.e. Vilsmeier reagent and dimethylformamide dimethylacetal, was investigated. These findings resulted in a revision of the reaction mechanism of Vilsmeier haloformylation and further contributed to understanding the chemical reactivity of this compound class. This study revealed that the reactivity is dependent upon a stereoelectronic effect arising from different ring conformations.

Improved optical character recognition by matched filtering

The effectiveness of linear matched filters for improved character discrimination in presence of random noise and poorly defined characters has been investigated. We have found that although the performance of the filter in presence of random noise is reasonably good (16 dB gain in signal-to-noise-ratio) its performance is poor when the unknown character is distorted (linear shift and rotation).