A quantitativestructureactivityrelationship (QSAR) is possible when sufficient data and enough compounds are available and the site of inhibition for all com pounds is identical. QSAR plays an im portant role for biologically active molecules, espe cially in drug design [ 3 8 ] . QSAR so far has been successfully applied for several groups of inhibitors of photosynthetic electron transport like substituted phenylam ides [3 9 , 4 0 ] , phenylcarbamates [ 4 1 ] , phenylureas [ 4 1 ] , anilides [ 4 1 ] , im idazoles [4 2 , 4 3 ] , and triaziones [ 4 4 ] . A sufficient quantitative correlation was obtained by using parameters for lipophilicity, like the partition coefficient P [ 4 4 ] , the acidity (pK a) of the com pounds under investiga tion [ 3 9 ] , or both together [ 4 2 ] . Additional pa rameters for electronic and steric effects seem to be of little relevance in the case of photosynthesis in hibitors so far investigated. QSAR of such a kind in simple cases can be expressed by a linear relation of the Hansch type [4 0 ] (Eqn ( 1 ))
A number of 16 substituted diphenylamines have been tested for their inhibitory activity on photosynthetic NADP reduction and photophosphorylation. The most active compounds exhibited p l50 values of 6.0 in photosynthetic electron transport and 6.8 in cyclic photophosphorylation, respectively. The inhibition site in electron flow of the diphenylamines is located between the two photosystems. Necessary for high activity is the substitution of the phenyl moieties by several strongly electron withdrawing substituents. A quantitativestructureactivityrelationship according to a parabolic Hansch approach could be accomplished by using the Hammett electronic parameter as the only variable.
Herbicidal activities were determined by a green house test. Avena, Setaria and Lolium were treated with aqueous suspensions of the compounds at concentrations of 4 kg/ha. The herbicidal activity given in Table II is the arithmetic mean of the ob servations (9 = --no activity, 1 = total kill) after post emergence application on the three weeds.
N ew 2-phenylpyridazinones, analogs o f 4-chloro-5-m ethylam ino-2-phenylpyridazin-3(2H )ones, were assayed for their phytotoxic activity to interfere with plant pigm ent formation. Six derivatives with — SC F3, — O C F2C H F C F 3, — O C H F 2, — C N , or — Br in m eta position o f the phenyl ring exhibited similar or better bleaching activity than the m -C F 3 analog (norflurazon). T he activity is predominantly determined by positive a values and by lip oph ilicity o f the substituent. On the basis o f 11 analogs, a quantitativestructure-activityrelationship by a Hansch equation was accom plished with am and the lip op h ilicity param eter n as variables.
Both products were used in an azo coupling reaction with salicylic acid (Scheme 12). Ketone 22a underwent azo coupling generating azobenzene 23 in 48 % yield. This intermediate was then deprotected in quantitative yield by alkaline hydrolysis of the ethyl ester to give the free carboxylic acid CG_64. Surprisingly, alcohol 22b did undergo the azo coupling reaction as well but in contrast to 22a the ethyl ester was cleaved simultaneously whereby hydroxyacid CG_65 was obtained in 36 % yield. Possibly the conditions were slightly more basic, which led to concerted hydrolysis of the ester. Important to note here is the observed instability of both amine 22b and azobenzene CG_65. Both compounds experience dehydration reactions (presumably to a styrene or lactone) among other decomposing reactions (22b to some extent slower). Therefore, these molecules have to be used for following reactions or tested shortly after preparation and biological results have to be interpreted with care.
2. Q SA R studies on peroxidizing herbicides
For a large number of compounds, it has been established that their herbicidal efficiency in greenhouse tests and growth-inhibition activity against Echinochloa can be quantitatively corre lated with high significance through the peroxida- tive phytotoxic parameters obtained from auto- trophic Scenedesmus cells (Böger and Wakabaya shi, 1995; Wakabayashi et al., 1988; Watanabe et al., 1992; Böger and Sandmann, 1994). Those are growth inhibition, decrease of chlorophylls and carotenoids, short-term accumulation of proto-IX and light-induced ethane formation, even the protox inhibition using corn etioplasts can be now combined with this network. A reli able quantitative correlation has been established with the six parameters mentioned. For example, QSARs of the peroxidizing compounds can be ac complished either with the Echinochloa root- growth inhibition test, by measuring light-induced ethane formation, or with decrease of chlorophyll content in sensitive green microalgae. The investi gator may choose any one of the six parameters, whichever he can handle best in the laboratory.
Both tables clearly demonstrate the loss of significance that occurs when applying the large data set instead of the small or the enlarged one. The impairment of statistical quantities like F- and q 2 -values takes place without being affected by the choice of parameters (i.e., literature or calculated parameters). As a matter of fact, a significant regression equation could not be established under application of the large data set. Critically revising the composition of the large data set (compounds 1-41, listed in table 7-1, chapter 7.4.2), it was once more analyzed whether the incorporation of the additionally methoxy-substituted paullone derivatives into the data set constituted a legitimate action. This time, a “dummy- parameter” was employed. Dummy-parameters, also called indicator variables, are commonly used in QSAR analyses to indicate merely the presence or absence of a substituent or substructure. Thus, a dummy- parameter represents a descriptor that can only assume the two values 1 or 0, depending on the presence or absence of a given condition. In the resulting regression equation, the t-value corresponding to the dummy- parameter then indicates whether the examined condition makes a significant contribution to the established quantitativerelationship. 133 In this case, a methoxy group at the 3-position of the paullone molecules represented the structural feature to be characterized by the employed dummy-parameter. Analyses were performed with three different descriptor combinations under application of the large data set, utilizing the literature parameters as well as, in separate correlation calculations, the calculated parameters (cf. chapter 7.4.5, regression equations 161- 163 and 258, 259, and 261). The results are shown in table 4-5.
W . D ra b er • N e w PS-II In h ib itors by Q S A R and M o le c u la r G rap h ics? 715
A New Dimension in QSAR: Molecular Graphics
M olecular graphics has brought a n ew d im en sio n into m any aspects o f the relationship b etw een c h e m i cal structure and b iological activity, in m ore than o n e resp ect. B y this procedure it b e c o m e s p o ssib le to tackle the problem o f how con form ation and size o f a m o lecu le affect the b iological activity and to visu alize this in three d im en sion s. T he input for m olecu lar m o d ellin g usually co m es eith er from X -ray crystal lography or, if not availab le, from quantum and m olecu lar m echanics calcu lation s. T h ese do n ot on ly n eed an exp ert, th ey are also C P U -tim e co n su m in g , esp ecia lly w hen th ey have to be applied to larger m o lecu les or p ep tid es. A n ad d ition al increase in com p u ter tim e is required if con form ation al m ob ility m ust be accou n ted for. T here are sev era l com m ercial program m es on the softw are m arket that allow not on ly a m u lticolored , th ree-d im en sio n a l display o f structures but also o f surfaces, d ifferen t charge d e n sities and oth er structural featu res. M o reo v er, it is p ossib le to show in o n e picture a m u ltitu d e o f fa v o u r able con form ation s o f o n e or m ore m o lecu les at th e sam e tim e. T he docking o f effecto r m o lecu les to its recep tor can be d em on strated , although for such p u rp oses gen erally an X -ray structure o f the recep to r is required. B eca u se this tech n iq u e em p h a sizes steric relation sh ip s b etw een effecto r m o le c u le s and r e c e p tors, o n e cannot ex p ect p red iction s p oin tin g tow ards sp ecific substitution as in the H an sch approach. Its predictive pow er is o f another quality. T o nam e o n e advantage o f m olecu lar graphics: q u ite o ften it is p o ssib le to d etect sim ilarities b etw een tw o or ev en m ore chem ical classes o f effectors that lo o k d ifferen t on th e p aper, provided — o f cou rse — th ey act by the sam e m olecu lar m echanism . From this m ay result an oth er class o f active co m p o u n d s by a kind o f “cro ssin g ” o f the p revious on es.
Seth and colleagues (Seth et al., 2005) found a relationship between trauma, PTSD and features of borderline personality disorder. Another study conducted in 1993 by Southwick, Yehuda and Giller (1993), with 18 inpatients and 16 outpatients, found that at least one third of them suffered from at least one personality disorder. The most common personality disorder to be diagnosed with was borderline personality disorder in 76% of the cases, obsessive compulsive personality disorder was diagnosed in 44% of the cases, avoidant personality disorder in 41%, and paranoid personality disorder in 38% of the cases (Southwick et al., 1993). Inpatients were generally more often diagnosed than outpatients. The results from the above mentioned studies demonstrate that prolonged exposure to traumatic events, is not only capable of causing variations in personality factors, but their effects could be as severe as to play a major role in the development of certain personality disorders as well. The main symptoms of the borderline personality disorder, paranoid personality disorder and avoidant personality disorder are related to the experience of high anxiety in social interactions (Davey, 2008), and as a result, poorer social interactions, and decrease in their frequency. Our finding that trauma reduces our positioning on extraversion and agreeableness also reflects a poorer quality of interpersonal functioning and performance.
New Peroxidizing Herbicides: Activity Compared with X-Ray Structure
Hitoshi K ohno, Kenji H iraia, M asahiro H orib, Y ukiharu Sato, Peter Bögei^, and K o W akabayashi T am ag aw a U niversity, T o k y o , J a p a n
a Sagam i C hem ical R esearch C enter, K a n ag aw a, Ja p a n b K ak en P h arm aceu tical C o. L td., T o k y o , Ja p a n c U n iv e rsitä t K o n sta n z , B undesrepublik D eutschland
The study was conducted in July and August 2016 during the examination period, which represents a natural stressor for students. Participants were invited to the laboratory and were informed about the purpose and procedure of the study. Next, they signed an informed consent to take part in the study. Afterwards, they completed demographic variables (e.g., age, gender), and a battery of psychological questionnaires on an online survey platform 2 . Then, participants were supervised for the installation of the PsyDiary app. Furthermore, important information for the use of the devices and the EMA items was provided and participants completed three practice trials in the presence of a research staff member to clarify their use. Moreover, participants received an app manual with a summary of the important information and contact details in case of any disturbances or questions. The first day was a practice day, and these data were not included in the analyses. Thus, participants became acquainted with the app and had the opportunity to ask questions arising in relation to the technique, app, and/or items. After this practice day, participants reported their affect, stress, physical activity, and eating behaviour during 7 days. More specifically, a signal-contingent sampling was used, prompting participants every 2.5 hrs (9 a.m., 11.30 a.m., 2 p.m., 4.30 p.m., 7 p.m., 9.30 p.m.). Data segmentation was chosen to balance between obtaining sufficient data within the short study period, without overwhelming participants during their examination period. A 1-hr time window was available to complete each assessment, with reminders every 10 min. If the participants did not reply within 1 hr, the current signal resulted in a missing value. In case of low compliance (meaning no answer of 50% signals daily) during this period, participants were contacted by the experimenter to remind them about signal completion. At the end of 1 week, students completed questions about reactivity and compliance and received monetary compensation of 25 € or three course credit points.
A STEM image from the tilt-series (Figure 3.2a) gives some idea of the disordered morphology of the investigated mesoporous carbon. After 3D reconstruction, the internal mesopore structure is better revealed with the irregular shape and non-uniform size visible in the slice (Figure 3.2b). Segmenting the 3D reconstruction is an indispensable step to provide any quantitative 3D structural information. As indicated in section 3.2.3, the SIRT reconstruction and the DART reconstruction were segmented to provide quantification information on the morphology of the investigated material. Figure 3.2c and d show the segmented 2D slices of the segmented-SIRT and the DART reconstruction. Visually, most of the features are presented in the segmented slices compared to the initial SIRT reconstruction slice (Figure 3.2b). However, when looking closely at the highlighted regions, there are still differences in the size (red circles) and 2D connectivity (blue circles) of some pores, indicating imperfections in the segmentation. To evaluate the fidelity of the segmented reconstructions, the re-projection tilt-series generated from the segmented-SIRT and DART reconstruction are compared with the experimental tilt-series (Figure 3.3). The difference between the experimental projections and the re-projections were estimated by MAE calculation, where the MAE was calculated for the nine re-projection directions shown in Figure 3.3d. The result indicates that the MAE values of the segmented-SIRT reconstruction are slightly larger than the DART reconstruction. However, it is hard to tell which reconstruction is better from the MAE calculation because the differences are so small.
bands associated with the vibrational modes of Li‒O bonds are possibly located in the very low Raman shift region since Li‒O interatomic distances are very large, and it may be well possible that the bands are situated below the detection limit (≤ 80 cm -1 ) of this instrument. The temperature-dependent Raman shift for selected W‒O bonds show most of the vibrational modes become harder at low-temperature conditions; however one of the W‒O stretching mode (about 705 cm -1 at 78 K) shows right Raman shift (Figure 3.13). It indicates that one particular W‒O bond is becoming harder while the material is heated up from liquid-nitrogen temperature to room-temperature. Temperature-dependent Raman data also demonstrate that there is a phonon modes anomaly from 205 K to 250 K as shown in Figure 3.13 (light dotted lines). The reason for such anomaly is still unknown. It may be due to the thermal phonon decay or inter-octahedral rearrangement within the structure. Temperature-dependent X-ray powder diffraction data Rietveld refinements results also show an anomaly for the lattice parameters change within this temperature range.
As mentioned before, in 2002 Shen and co-workers reported new homoleptic lanthanide amidinates and their catalytic activity for the ring-opening polymerization (ROP) of - caprolactone at room temprature . Thus far, the lanthanide amidinate and guanidinate complexes have witnessed rapid progress and have been proven to be very efficient homogeneous catalysts/precatalysts in organic transformations and polymerizations e.g. for the guanylation of amines or the ring–opening polymerization of lactones [22, 40]. The lanthanide amidinate complexes were found to effectively catalyze the addition of various primary and secondary amines as well as aromatic and aliphatic diamines to carbodiimides to afford the corresponding monoguanidine and biguanidine derivatives . Guanidines are important structure motifs found in many biological and pharmaceutically active compounds [53, 54]. Lanthanide amidinate compounds were also found to be excellent precatalysts for the addition of terminal alkynes to carbodiimides yielding a series of propiolamidines [165 170].
To conclude, companies are creating new flexible organizational forms that respond to their customers' needs and the market's requirements. “The key feature is the understanding of their customers' needs and the value offer to their customers” (Cravens et al., 1994, p. 19). As Achrol pointed out (1991, p. 80), "the firm of the future will need to be very permeable between its departments. Its departments and hierarchy will be confusingly defined, the hierarchy will be minimum and indirect and individuals will have much more autonomy". In this context, what emerges is a new form of organization based on a flexible network of independent organizations through vertical links with suppliers and users and horizontal links with competitors (Cravens et al., 1994). The consequences of these new designs can be difficult to understand and may even turn out to be contradictory. Hence, it has been noted that these networks may represent a problem to attain and maintain a market orientation and a customer focus . This is because the complexity associated with the networks can mean an obstacle for the employees to identify the end customers, as well as their requirements. Moreover, it can limit organizational learning (Cravens et al., 1996). The organizational structure can be described on the basis of different variables, though the literature (Aiken and Hage, 1966; Hall et al., 1967; Zaltman et al., 1973; Champion, 1975; Evers et al., 1976; Van de Ven, 1976; Dewar and Hage, 1978; Robbins, 1987a; Hall, 1996) indicate formalization, centralization and complexity as its fundamental and commonly-studied dimensions. A fourth component – integration -tends to be added to these factors (Lawrence and Lorsch, 1967; Galbraith, 1973; Mintzberg, 1998).
amide content is observed due to amorphous amide segments. Upon heating above the melting temperature of the hard domains, the polymer forms a homogeneous melt which can be easily processed. On cooling segregation between the hard and soft domains takes place. Segmented PEAs can be synthesized by replacing part of one of the reactants in polycondensation by a preformed amide containing monomer of uniform structure. Preformed monomers such as bisamide-diols or bisamide-diesters can be aliphatic or aromatic in nature. Tailor made monomers such as bisamide-diols and bisamide-diesters can be condensed with diols and dimethyl adipate to yield segmented PEAs. 84-91 The uniform amide blocks are randomly distributed in the polyester backbone. The polymers show one glass transition temperature which increases with increasing amide content. This proves the presence of one homogeneous amorphous phase. Bisamide-diol, prepared from 1,6- hexanediamine and γ -butyrolactone, was reacted with adipic acid to form a hard PEA segment and a soft oligoester segment was obtained from 1,2-ethanediol and adipic acid. 91-93 A series of PEAs was obtained by reacting various ratios of these hard and soft oligomeric segments. In this case, two separate glass transition temperatures and one melting temperature were observed, indicating the presence of two distinct amorphous domains and one crystalline phase.
Once each of the main structural variables has been independently studied and taking into account that these factors make up an integrated system (Mintzberg, 1998), we consider it relevant to comment on the effect of them in an aggregated manner as a conclusion. It has been suggested that organizations with high levels of formalization and centralization and low specialization would be more efficient, although it is possible for them to turn out to be less innovative and adaptable (Walker and Ruekert, 1987). On the other hand, the literature on subjects of organizational behaviour notes that the organizations that are more decentralized and less formalized probably have a greater information use (Zaltman et al., 1973; Deshpandé, 1982; Deshpandé and Zaltman, 1982).It is thus pointed out that in a more structured organization (in terms of formalization and centralization) information use is reduced (Menon and Varadarajan, 1992), while the flexibility to adapt itself to changes in the environment is less (Ruekert et al., 1985). The results attained by Avlonitis and Gounaris (1999) in a sample made up of 444 Greek firms clearly show that companies that count on an informal organizational scheme maintain a decentralized structure and show a greater risk tolerance. They also have a positive attitude toward market orientation and present a market-oriented behaviour.
ficantly affected which is in agreement with the crystallographic studies . On the other hand, the on-copper conformation of TPQ/TYR-466 found in the mutant X- ray structures is not retained during the production run and rather switches between the on and the off-copper conformation in case of both the mutants. This observa- tion re-emphasizes the fact that the conformational subspace which is sampled in a crystal structure can be significantly different from that sampled in solution. The TPQ-466 in case of wild-type was found to be in the off-copper conformation during most of the production simulation. The analysis of φ and ψ dihedral distribution of TPQ/TYR-466 in wild-type, E573Q and E573Q/I342F mutants indicate a sim- ilar conformational subspace explored by TPQ/TYR-466 in case of wild-type and double mutant. In case of E573Q mutant, this residue is found to be more flexible and explores a larger conformational subspace. This result is in a general agree- ment with the THz-TDS measurements on the crystals of ECAO which indicate an increase in the absorption coefficient of the single (E573Q) in comparison with the double (E573Q/I342F) mutant and wild-type ECAO, indicating an increase in the dynamics of E573Q mutant of ECAO on picosecond-to-nanosecond time scale . We could also observe a change in the correlated dynamics of TPQ/TYR-466 and TYR-381 such that the C α -C α distance between these residues reduces significantly in the case of the two mutants leading to a reduction in the solvent accessibility to the active site. This can be directly correlated with a ≈ 3 fold reduction in hydration number of TPQ/TYR-466 in the case of the mutant enzyme systens. This result can be one of the explanations for the drastic reduction in the activity of the two mutants of ECAO. These observations indicate that the local, internal and global diffusive dynamics of ECAO in case of E573Q and E573Q/I342F mutants are significantly affected.
In order to model the dynamic interplay between couples, we used a structural equation modeling approach for lon- gitudinal data (Bolger & Laurenceau, 2013 ; Cole & Max- well, 2003 ). Our basic model included the regressions of all outcome variables of interest (male and female sexual desire, male and female relationship quality, and an indicator whether the couple had sex) on the corresponding variables measured at the previous occasion. The couple was the main unit of analysis, with male and female responses nested with- in the couple. To examine the main study questions, we relied on the Actor Partner Interdependence Model (APIM) which provides a simultaneous test of actor and partner main effects (Kenny, Kashy, & Cook, 2006 ). All predictor variables had to be lagged because the questions on sexual desire and sexual activity were completed in the morning and were thus coded as the following day, while relationship quality of that day was coded as the previous day. This implies that the temporal association between desire and sex was defined as a Lag 1 effect, whereas the temporal associations including relation- ship quality were defined as Lag 2 effects. To ensure a correct understanding of our results, we simplified the description of the effects such that t1 refer to scores on relationship quality, desire, and sexual activity on a previous day. Figure 1 shows a path diagram of our final model, illustrating the effects of our basic model. Variables were grand-means centered, thereby assuming that the within-person effects were the same as the between-person effects. We used a logistic re- gression for the submodel with sexual activity as the depend- ent variable. All regressions were estimated simultaneously using robust maximum likelihood with corrected standard errors (SE) for clustered observations in Mplus 7 (Muthén & Muthén, 1998 –2012). In a second step, we extended our basic model to investigate whether the effects changed depend- ing on potential moderators, namely relationship duration,