2 3 Blood Sample Collection; Method of Measurement Blood samples

2.3 Blood Sample Collection; Method of Measurement Blood samples were collected into tubes containing K2-EDTA prior to and 0.33, 0.67, 1, 1.33, 1.67, 2, 2.5, H 89 nmr 3, 3.5, 4, 5, 6, 8, 12, 16, 24, 36, 48 and 60 h after drug administration. This sampling was planned in order to provide a reliable estimate of the

extent of absorption, as well as the terminal elimination half-life, and to ensure that the area under the plasma concentration–time curve (AUC) from time zero to time t (AUC t ) was at least 80 % of the AUC from time zero extrapolated to infinity (AUC ∞ ). Samples were processed and stored under conditions (frozen) that have been shown not to cause significant degradation of the analyte. The experimental samples

were assayed for doxylamine, using a validated bioanalytical ultra-high-performance liquid chromatography method with tandem mass spectrometry detection (UPLC/MS/MS method, Xevo TQ MS, Waters Corp., Milford MA), which involved the solid-phase extraction of doxylamine and the deuterium-labeled internal standard (Doxylamine-d5) from plasma samples (150 μL). The calibration curve ranged from 1.0 to 300.0 ng/mL and the limit of quantification was 1.0 ng/mL. A gradient elution with 0.1 % formic acid in acetonitrile and 0.1 % formic acid in water was used for the mobile phase. A volume of 10 μL was injected into an Acquity UPLC Doramapimod BEH C18 column (1.7 μm learn more particle size, 2.1 mm id × 50 mm length) and the transitions (m/z) for both doxylamine (271.22/167.02) and internal Phospholipase D1 standard (276.24/171.28) were monitored using MRM ion mode ESI+. The parameters evaluated during the validation were linearity and range, selectivity including hemolysed and hyperlipidemic plasma, specificity in the presence of common OTC, intra- and inter-run precision and accuracy, limit of quantification, dilution integrity,

carryover, recovery, matrix effect, stock solution stability, autosampler stability, short-term stability in human plasma at room temperature, freeze-thaw and long-term stability in human plasma. All the evaluated parameters met the acceptance criteria of the current guidelines. For past analytical batches run during the validation, the precision expressed as %CV of calibration standards ranged from 0.8 to 3.7 %, and the % mean accuracy of the back-calculated value of the calibration standards ranged from 94.2 to 103.4 %. The mean correlation coefficient for these analytical batches was 0.9992. The intra-run precision expressed as %CV for all concentration levels of quality control samples ranged from 0.9 to 12.7 %, and the inter-run precision ranged from 1.1 to 7.9 %. The intra-run accuracy expressed as % nominal for all concentration levels of quality control samples ranged from 96.4 to 113.7 %, and the inter-run accuracy ranged from 102.8 to 108.8 %.

Additionally, IP6 has shown a significant anticancer effect again

Additionally, IP6 has shown a significant anticancer NCT-501 cell line effect against different experimental cancers [3–15]. For some time, IP6 is available as a dietary supplement. Although few case studies in which IP6 plus inositol was given in combination with chemotherapy clearly showed encouraging data, organized,

controlled, randomized clinical studies were never organized [16–18]. Therefore, this study conducted at the Department of Surgery, General Hospital, Zadar on the group of voluntary patients who were treated for breast cancer, is the first study of its kind in the world. From this small clinical testing we concluded that IP6 + Inositol was able to improve the quality of life of breast cancer patients AR-13324 molecular weight undergoing chemotherapy compared to control, placebo group with the same histological type of cancer and the therapeutic protocol. It is difficult to be objective and to numerically express the quality of life of individual patients or groups of patients selleck chemicals in order to compare the quality of life of another patient, because it depends on a number of parameters. The European Association for research and treatment of cancer (EORTC) has developed questionnaires

for assessing the quality of life of patients which have fallen ill from cancer, and thus tried to compare objectively the quality of life that we utilized. Our results show that patients who were taking IP6 + Inositol in combination with chemotherapy, had overall statistically significantly better quality of life than patients who were on placebo. Analyzing the answers to questions about the side effects of treatment and symptoms of disease, we have seen that the frequency and intensity of side effects associated with patients who were taking IP6 + Inositol were statistically significantly lower in comparison to patients who were taking placebo. Florfenicol Drugs that are implemented in chemotherapy are agressive and have impact to the tumor cells as well as to the cells in

the blood. Most patients who are undergoing chemotherapy have some anomalies in their complete blood count, primarily in the number of leukocytes and plateletes. Our results show that patients who have taken IP6 + Inositol did not show drop in the number of leukocytes and plateletes, on the contrary, these were even slightly increased. A slight increase in red blood cell counts and hemoglobin levels were also noticed in the IP6 + Inositol group. Tumor markers, liver enzymes, bilirubin, urea, creatinine and electrolytes were not disturbed in either group during the 6-month period of treatment. Although our clinical study was conducted on a small number of patients, our results confirmed previous observations and clearly demonstrated that IP6 + Inositol when included in chemotherapy for breast cancer significantly improved patients’ quality of life and protected patients from the loss in the number of leukocytes and plateletes [16–18].

intermedia since a genetic transfer system for having gene-target

intermedia since a genetic transfer system for having gene-targeted mutants of this organism yet remains to be developed [47, 48]. However, recent studies evidently showed a tight relation between stress responses and click here biofilm formation [46, 49–55], though stress response genes are not prominently up-regulated in some experimental biofilm

formation [56]. We found in our earlier study that exposing biofilm-positive P. intermedia to environmental stress such as animal passages of the organism resulted in the up-regulations of HSPs at a protein level with increased production of cell surface-associated meshwork-like structures. By contrast, animal passages induced neither the production of viscous materials nor the up-regulation of HSPs in strain 17-2 (unpublished data). When we compared the gene expression I-BET151 profiles of strain 17 cells plated on BAPs to those of planktonic cells in enriched-TSB, transcriptional levels of several genes including those for a levanase (ScrL: PINA0149), putative σE (PINA0299) and a polysialic acid transport protein (KpsD: PINA1911) were dramatically up-regulated ZD1839 on cells from the solid culture media. The highest transcriptional level was observed on a hypothetical protein (PINA1526) with LTXXQ motif which is found in a number of bacterial proteins bearing similarity

to the protein CpxP [57]. PINA0299 (putative σE) is homologous to the gene for AlgU which affects the conversion to buy AZD9291 mucoidy and alginate production in P. aeruginosa [58]. The AlgU (σE)-dependent promoter of RpoH, well known positive regulator of heat shock genes, is known to be activated in mucoid type P. aeruginosa [58]. Although plating of planktonic cells at an exponential phase itself is known to immediately induce the expression of heat shock regulons in E. coli [59], we now hypothesize that, like AlgU (σE) in P. aeruginosa [58], P. intermedia strain 17 cells keep their stress response via one of ECF sigma factors activated;

thus rendering this organism to maintain EPS production at high levels in different growth conditions. However, so far we studied, gene clusters responsible for mannose-rich EPS still remain to be elucidated. To address the question of whether the gene expression phenomena observed in this study represent gene expression events behind the EPS production in P. intermedia biofilm, operon/genes for EPS synthesis regulated by stress-responsive systems of this organism must be explored in future studies. Conclusion The data obtained in this study suggest that the Prevotella biofilms mainly composed of mannose-rich polysaccharides contribute to their resistance to host innate defence responses resulting in the development of chronic infections in vivo, and may also suggest that stress responsive systems of this organism might be behind its biofilm formation. To figure out a biofilm formation-gene expression relay system in P.

Br 028/029 B F0678 Shida Kartli Kaspi village z/Rene Dermacentor

Br.028/029 B F0678 Shida Kartli Kaspi village z/Rene Dermacentor marginatus 06/00/2008

B.Br.028/029 C F0679 Shida Kartli Kaspi village z/Rene Haemaphysalis sulcata 06/00/2008 B.Br.028/029 D F0659 Kvemo Kartli Dmanisi unknown Microtus arvalis Pall. 00/00/1990 B.Br.029/030 A F0665 Shida Kartli Gori village Shavshvebi Gamasidae ticks 00/00/1982 B.Br.029/030 A F0666 Samtskhe-Javakheti Aspindza village Indusa Dermacentor marginatus 00/00/2004 B.Br.029/030 A F0667 Shida Kartli Gori village Nadarbazevi Dermacentor marginatus 00/00/2004 B.Br.029/030 A F0668 Shida Kartli Gori village Nadarbazevi Dermacentor marginatus 00/00/2004 B.Br.029/030 A F0669 Samtskhe-Javakheti Ninotsminda unknown selleck products Dermacentor marginatus 00/00/2002 B.Br.029/030 A F0670 Shida Kartli Gori village Tkviavi Dermacentor marginatus 00/00/2004 B.Br.029/030 A F0672 Shida Kartli Gori village Khurvaleti Dermacentor marginatus 00/00/2004 B.Br.030/031 E F0655 Kakheti Dedoplis Tskaro Solukh steppe Meriones erythrurus Gray 00/00/1956 B.Br.031/032 E F0656 Kakheti Dedoplis Tskaro Nazarlebi Mountain Ixodidae tick 00/00/1956 B.Br.selleck screening library Georgia E F0657 Shida 4SC-202 datasheet Kartli Tskhinvali village Khetagurov Sorex sp. 00/00/1974 B.Br.Georgia E F0661 Samtskhe-Javakheti Akhaltsikhe village Klde Microtus socialis Pall. 00/00/1992 B.Br.Georgia E F0663 Shida Kartli Kareli village Ruisi Ixodidae tick

00/00/1997 B.Br.Georgia E F0664 Shida Kartli Kareli village Ruisi wheat 00/00/1997 B.Br.Georgia E F0671 unknown unknown East Georgia unknown unknown B.Br.Georgia E F0673 unknown unknown East Georgia unknown unknown B.Br.Georgia E F0676 Shida Kartli Gori village Nadarbazevi Dermacentor marginatus 05/00/2007 B.Br.Georgia E a Strain ID in

the Northern Arizona University DNA collection b City, Town, or Village c canSNP lineage d Genotypes (A to E) determined by MLVA11 system (Vogler et al, 2009). Figure 2 Subclade Baf-A1 phylogeny and geographic distribution. (A) CanSNP phylogeny of the Georgian subclades within the Br.013 group. Terminal subclades representing sequenced strains are shown as stars and intervening nodes representing collapsed branches are indicated by circles. Newly identified branches are indicated in red and previously published branches are indicated in black. The right vertical black bars indicate the subclades that comprise the two major lineages within the B.Br.013 group. The number of isolates (n), MLVA genotypes (G), and a number in quotations to digitally represent each Georgian subclade on the distribution map. Dashes (- -) indicate hypothetical branch lengths for collapsed nodes. (B) Distribution of Georgian lineage subclades in the country of Georgia. The global geographic map indicates Georgia colored as red (lower left) and dashed lines show an enlarged map of Georgia at the district scale. Subclade and MLVA genotypes for each isolate are shown alphanumerically.

To look for differences in pathogenic potential, these 29

To look for differences in pathogenic potential, these 29 isolates were assayed for their ability

to invade Caco-2 epithelial cells. To correlate any differences in pathogenic potential with genomic variation we exploited a pan-Salmonella microarray for CGH. Six other S. Enteritidis isolated from distant parts of the world were included in the CGH analysis to compare the diversity seen in Uruguay with that found elsewhere. Results and Discussion Genotyping assays All 266 S. Enteritidis isolates (Table 1) were subjected to RAPD-PCR analysis using 5 different primers and GSK126 molecular weight were compared to S. Enteritidis phage type 4 (PT4) strain P125109. The complete sequence of S. Enteritidis PT4 P125109 has been determined and it acts as the reference for all the analyses reported here [27]. Table 1 Uruguayan find more S. Enteritidis isolates included in this study.   ISOLATION PERIOD Sample origin Pre-epidemic epidemic Post-epidemic TOTAL Faeces 1 112 22 135 Blood 1 34 6 41 Urine 0 2 1 3 Spinal fluid 0 3 1 4 Other 0 9

2 11 Subtotal human 2 160 32 194 Food* 4 39 8 51 Animal 0 12 1 13 Feed 0 7 1 8 Subtotal non-human 4 58 10 72 TOTAL 6 218 42 266 *Includes eggs and other products used for human consumption. Of the S. Enteritidis isolates tested in this study 96% showed the same amplification pattern as S. Enteritidis PT4 P125109 with all primers using RAPD-PCR. Only 10 isolates (3.8%) showed differences in the amplification pattern obtained with at least 1 primer. Thirty-seven isolates from different origins, periods and RAPD types, were subjected to PFGE after cleavage of their DNA with XbaI. Of these, 26 Vadimezan ic50 generated a restriction pattern identical to S. Enteritidis PT4 P125109, whereas 11 showed subtle differences (1 to

3 different bands, corresponding to 96 to 91% identity with S. Enteritidis PT4 P125109). When both typing methods were considered together, 21 out of the 37 isolates were indistinguishable Niclosamide from S. Enteritidis PT4 P125109, while 5 differed by both methods and 11 differed by a single typing method. The 5 isolates differing by both methods included the 2 oldest pre-epidemic isolates (31/88 and 8/89), 2 isolated from food (206/99 and 32/02) and 1 isolated from human blood (214/02). Overall these results revealed a high degree of genetic uniformity within S. Enteritidis circulating in Uruguay, with the great majority of isolates belonging to the same genetic profile as S. Enteritidis PT4 P125109. Next, 29 isolates were selected with the aim of maximizing the chances of finding divergence among the isolates. For this, we selected isolates that span the pre-epidemic, epidemic and post-epidemic periods in Uruguay and that cover any particular profile found in the RAPD and/or PFGE assays, and all possible sources of isolation (Table 2). The selected isolates were subjected to further phenotypic and genotypic characterization.

Octamer 4 (Oct-4), a member of the POU-domain transcription facto

Octamer 4 (Oct-4), a member of the POU-domain transcription factor family, is normally expressed in both adult and embryonic stem cells [3, 4]. Recent reports have demonstrated that Oct-4 is not only involved in controlling the maintenance of stem cell pluripotency, but is also specifically responsible for the unlimited proliferative potential of stem cells, suggesting that Oct-4 functions as a master switch during differentiation of human somatic cell [5–7]. Interestingly,

Oct-4 is also re-expressed in germ cell tumors [8], breast cancer [9], bladder cancer [10], prostate cancer and hepatomas [11, 12], but very little is known about its potential function in malignant disease [13]. Moreover, overexpression of Oct-4 increases the malignant

E7080 manufacturer potential of tumors, and downregulation of Oct-4 in tumor cells inhibits tumor growth, suggesting that Oct-4 might play a key role in maintaining the survival of cancer cells [13, 14]. Although its asymmetric expression may indicate that Oct-4 is a suitable target for therapeutic intervention in adenocarcinoma and bronchioloalveolar carcinoma [15], the role of Oct-4 expression in primary NSCLC has remained ill defined. To address this potential role, we assessed Oct-4 expression in cancer specimens from 113 Protein Tyrosine Kinase inhibitor patients with primary NSCLC by immunohistochemical staining. We further investigated the association of Oct-4 expression in NSCLC tumor cells with some important clinical pathological indices. In addition, we examined the involvement of Oct-4 in tumor cell proliferation and tumor-induced angiogenesis in NSCLC by relating Oct-4 expression with microvessel density (MVD), and expression of Ki-67 Ketotifen and vascular endothelial growth factor (VEGF), proliferative and the vascular markers,

respectively. On the basis of previous reports that a subset of NSCLC tumors do not induce angiogenesis but instead co-opt the normal vasculature for further growth [16, 17], we also evaluated associations of Oct-4 expression with tumor cell proliferation and prognosis in subsets of patients with weak VEGF-mediated angiogenesis (disregarding the nonangiogenic subsets of NSCLC in the analysis, which would tend to ON-01910 obscure the role of Oct-4 expression in primary NSCLC). Our results provide the first demonstration that expression of the stem cell marker Oct-4 maintains tumor cells in a poorly differentiated state through a mechanism that depends on promoting cell proliferation. Moreover, even in the context of vulnerable MVD status and VEGF expression, Oct-4 plays an important role in tumor cell proliferation and contributes to poor prognosis in human NSCLC.

Protein Kinase Activity Eighty cell permeable and ATP competitive

Protein Kinase Activity Eighty cell permeable and ATP competitive protein kinase inhibitors were purchased from EMD (San Diego). Each compound in the InhibitorSelect protein kinase library was screened at 10 μM (unless otherwise noted) in an in vitro PknD autophosphorylation assay. Briefly, each reaction contained 100 ng GST-PknD KD, 20 μM ATP,

5 mM MnCl2 and 3 μCi [γ-32P]-ATP in 25 mM HEPES buffer Inhibitor Library cost (pH 7.1) supplemented with 1× complete EDTA-free protease inhibitors, unless otherwise noted. Reactions were incubated for 90 min. at 33°C, terminated with SDS-PAGE loading buffer, separated by 10% SDS-PAGE and transferred to polyvinyldinedifluoride (PVDF) membrane. Membranes were exposed to Kodak X-OMAT film for 1-12 hours at -80°C and subsequently MK 8931 price developed using an X-ray processor. ATPase Activity ATP hydrolysis by GST-CdsN purified from glutathione-agarose beads was measured using a malachite green assay (R & D Systems). Reaction mixtures contained 100 ng of GST-CdsN, 4 mM ATP, 50 mM Tris-HCL pH 7.0, 5 mM MgCl2, and 10 mM KCl. Compound D7 was added to final concentrations of 1 μM, 5 μM, 10 μM and 100 μM. The reaction mixture (50 μL) was incubated at 37°C for 30 min. The reaction was stopped by the addition of 10 μL of Malachite Green Reagent A followed by 10 μL of Malachite Green Reagent B and incubated at room temperature for one minute before an OD610 reading was taken, according

to the manufacturer’s instructions. Immunofluorescent Microscopy MEK phosphorylation and Chlamydia Growth Experiments HeLa cells

(1 × 105) on coverslips in shell vials were infected with C. pneumoniae CWL029 (MOI of 1) using centrifugation, and replacement media containing 2 μg/mL cycloheximide was added Low-density-lipoprotein receptor kinase at 1 hpi. Protein kinase inhibitors (compounds D4, D5, D6 and D7) were added to the replacement media to a final concentration of 10 μM (unless otherwise noted), for the duration of the Chlamydia developmental cycle (72 hours). For time course immunofluorescence (IF) experiments, compound D7 was added at 1, 15 and 24 hpi. For IF staining cell monolayers were fixed in methanol for 10 minutes at 72 hpi for C. pneumoniae and at 48 hpi for C. trachomatis. Inclusions were stained with the Pathfinder reagent, a FITC-conjugated anti-LPS monoclonal antibody (Bio-Rad, Mississauga) containing Evan’s Blue counterstain. Images were captured at 400× magnification using an Olympus BX51 fluorescent microscope equipped with a color camera (Q color 5; Olympus). To determine the infectivity of Chlamydia grown in the presence of inhibitors, HeLa cells were infected with C. pneumoniae CWL029 and grown for 72 or 84 hrs in the presence of various compounds (used at 10 μM) or vehicle (DMSO 0.1%) then cells were lysed with glass beads into fresh MEM. Serial dilutions of lysates were used to infect fresh HeLa cells and inclusions were stained at 72 hr as described above.

(B) miRNAs that are differentially expressed

(B) miRNAs that are differentially expressed between NSCLCs and HBECs. (C) miRNAs that are differentially expressed between SCLCs and NSCLCs. Yellow indicates relative over-expression, MGCD0103 molecular weight and blue indicates relative under-expression. The miRNA expression profile changes progressively from normal cells to NSCLC to SCLC cells Interestingly, the above analysis indicates that more miRNAs are differentially expressed between SCLC cell lines and HBECs than between NSCLC cell lines and HBECs. In addition, the two miRNAs that are significantly differentially expressed in NSCLCs relative to HBECs

are included in the group of 30 miRNAs identified as differentially expressed in SCLCs relative to HBECS, as shown in Figure 2A. This suggests a possible pathological relationship between the three groups of cell lines. To examine this relationship, we applied linear LY2109761 manufacturer discriminant analysis to the three groups of cell lines based on the 41 miRNAs that are identified as significantly differentially expressed as shown in Figure 2. As shown in Figure 3, 88% of the between-group LY3023414 chemical structure variance is explained by the first discriminant function with miRNA expression placing NSCLCs between HBECs and SCLC lung tumor

cells, suggesting a progressive change in expression from HBECs to NSCLC to SCLC cell lines. Figure 3 A sequential change in expression profile from normal cells to NSCLC cells to SCLC cells. Linear discriminant analysis places the NSCLCs between SCLCs and HBECs, suggesting a progression from HBECs to NSCLC to SCLC cell lines. The plot is a projection of the multi-dimensional space into two dimensions described by two linear discriminants, in which the very individual points represent the cell lines

and the classifiers are indicated by black lines. 88% of the between-class variance is explained by the first discriminant function (displayed along the x-axis of the plot). To examine this relationship at the level of individual microRNAs, we applied the Jonckheere-Terpstra test for ordered means to the expression levels of each miRNA in the three groups. This allowed us to assess whether or not the expression trend followed the order SCLC, NSCLC, HBEC. As shown in Table 2, of the 26 miRNAs that are over-expressed in SCLC cell lines relative to non-SCLC cell lines, all 26 (100%) show ordered expression at a significance level of 0.05, with 24 (92%) showing strict ordering of mean expression levels with SCLC > NSCLC > HBEC. Of the 15 miRNAs that are under-expressed in SCLC cell lines relative to non-SCLCs, 14 (93%) show ordered expression at a significance level of 0.05, with 10 (66%) showing strict ordering of mean expression levels with SCLC < NSCLC < HBEC. These results suggest that expression of a set of miRNA changes progressively from normal cells to NSCLC tumor cells to SCLC tumor cells.

The initiative’s bid to fasten the mobilization of new biomedical

The initiative’s bid to fasten the mobilization of new biomedical knowledge in clinical innovation and align the innovation system towards patients needs seem directly inspired by the TR movement. The OncoTyrol consortium provides another SBI-0206965 purchase interesting instance to study the interplay between the TR model and national idiosyncrasies in biomedical innovation. The make-up of this consortium can

be traced back to local policy-makers’ Belnacasan in vivo long-standing concerns with technology transfer and the support of academia-industry joint projects. An early version of the consortium was first assembled as a regional Center of Excellence, created with the explicit purpose of fostering academia-industry exchanges. Yet, in this case, the regional cluster involved not into an incubator of start-up biotechnology firms as national orientations may have indicated, but rather into an instance of TR large-scale development collaboration, with strong means to exert a broad coordination of individual research teams. Here again, propositions from the TR model have inflected

local practices to create new organisational forms. In summary, important propositions from the TR model have certainly been implemented in the three countries studied. Yet previous institutional and policy developments have determined which components of the TR model have been taken up and which have not. Interestingly,

whereas policy-makers in Finland and Germany appear to be key actors in the implementation of the TR model, uptake Luminespib supplier is driven very much by local biomedical leaders and academic administrations in Carteolol HCl Austria. Conclusion Translational research has emerged as a major new approach for the organisation of biomedical innovation systems. This article has sought to determine the extent to which the proposals of TR advocates have effectively been implemented in policy and new initiatives in Austria, Finland and Germany. From the results and discussion presented above, it appears that national TR initiatives in our three countries have developed very much in extension of historical trends and structures of biomedical RTD capacities. Local academic administrations and policy-makers have drawn mostly from those components of international TR initiatives and narratives that extend previous institutional and experimental trajectories. Germany has seen rather intensive institutional and policy activity revolving around the proposals of TR. Finland shows mixed adoption, although participation in EU networks offers a unique pattern of engaging in large collaborations for the development of complex new health interventions. Austria has seen the establishment of a few important initiatives but comparatively little policy activity.

1983; de Groot et al 1985) For the ET from QA to QB a spin-cata

1983; de Groot et al. 1985). For the ET from QA to QB a spin-catalytic learn more role of the non-heme iron to facilitate spin-selective ET has been proposed

(Ivanov et al. 1999). In this concept ISC accelerated by the spin-catalytic active non-heme iron promotes the indirect ET from the triplet radical pair 3[QA −QB −] and therefore the product formation to 1[QAQB 2−]. One may selleck screening library assume that the phenomenon of the solid-state photo-CIDNP effect could be rationalized in terms of nuclear observer spins, on the one hand obtaining nuclear polarization, on the other hand providing a spin-catalyst for ET. Under natural conditions, however, the primary radical pair lives 200 ps, by far too short to allow for hf interaction. Hence, the effect cannot be the cause of the efficiency, but the assumed correlation between the parallel occurrence of effect and high efficiency may be based on common principles. There may be some until now unknown fundamental principles of photosynthetic charge separation and stabilization that leading to both phenomena. In that case, photo-CIDNP MAS NMR would be useful for studies GDC-0449 chemical structure in artificial photosynthesis for three reasons: (i) as an analytical tool, (ii) as heuristic guide based on the strength of the effect, and (iii) by the possibility for exploration of the fundamental principles.

These fundamental principles may be related to highly optimized constraints in geometry and ET kinetics as chosen

and conserved by nature. It has been pointed out PD184352 (CI-1040) that both the solid-state photo-CIDNP effect and the efficient light-induced ET require optimized overlap of the wavefunctions (Jeschke and Matysik 2003) corresponding to moderate electron–electron coupling parameters. A clear picture of the required architecture of orbitals, however, is still missing. Such concept of overlapping static orbitals of the cofactors would be sufficient for the microscopic description of both the ET and the coherent origin of the solid-state photo-CIDNP effect. On the other hand, understanding of both processes on the protein level would allow for including the dynamic role of energy dissipation and entropy production in the transfer of electrons and polarization. It is possible that both ET and the solid-state photo-CIDNP effect require optimized dissipation channels. The relevance of protein relaxation for photosynthetic ET has been stressed (Cherepanov et al. 2001). Under conditions of irreversible thermodynamics, self-organized ET, in which improved entropy management allows for active coupling of the ET to a matrix with non-linear response, may lead to negative friction and gating (Tributsch and Pohlmann 1998; Tributsch 2006). Hence, experiments mapping light-induced changes at the atomic resolution may provide the empirical basis for the determination of the origin of the parallel transfer of electrons and of electron polarization to nuclei.