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We present avidity sequencing, a sequencing chemistry that separately optimizes the processes of stepping along a DNA template and that of identifying each nucleotide within the template. Nucleotide identification uses multivalent nucleotide ligands on dye-labeled cores to form polymerase–polymer–nucleotide complexes bound to clonal copies of DNA targets. These polymer–nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides from micromolar to nanomolar and yield negligible dissociation rates. Avidity sequencing achieves high accuracy, with 96.2% and 85.4% of base calls having an average of one error per 1,000 and 10,000 base pairs, respectively. We show that the average error rate of avidity sequencing remained stable following a long homopolymer.

We present a novel sequencing chemistry implemented as part of the AVITI system. Relying on the proximal DNA binding sites created through DNA amplification on a solid support, avidity sequencing uses multivalent nucleotide ligands on dye-labeled cores to simultaneously form polymerase-polymer nucleotide complexes bound to clonal copies of DNA targets. These polymer-nucleotide substrates, termed avidites, decrease the required concentration of reporting nucleotides by 100x and yield a negligible dissociation rate. We demonstrate the use of avidites within a novel sequencing technology that surpasses Q40 accuracy and enables a diversity of applications that include single cell RNA-seq and whole human genome sequencing.

Ovarian cancer (OC) is the second leading cause of gynecologic cancer death in women around the world. N6-methyladenosine (m6A) is the most abundant internal modification on eukaryotic RNA. Human insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), as an m6A reader, can enhance mRNA stability and promote translation by recognizing m6A modifications. Its carcinogenic effect has been demonstrated in colon cancer, hepatocellular carcinoma, pancreatic cancer and other tumors. Here, we demonstrated that there was widespread dysregulation of m6A modification in OC tissues. The m6A modification, mRNA and protein level of IGF2BP2 were significantly elevated in OC. Overexpression of IGF2BP2 facilitated OC cell proliferation, migration, invasion in vitro and accelerated tumor growth and metastasis in vivo. Mechanistically, CKAP2L was a target mRNA of IGF2BP2. Unlike previous studies, IGF2BP2 promoted CKAP2L translation depending on m6A modification rather than affect mRNA and protein stability. Knockdown of CKAP2L rescued the oncogenic effect of IGF2BP2 in OC cells. In conclusion, this study unveiled the oncogenic role of IGF2BP2 potentially through promoting the translation of CKAP2L in a m6A dependent manner.

Background Circular RNA (circRNA), a class of RNA with a covalent closed circular structure that widely existed in serum and plasma, has been considered an ideal liquid biopsy marker in many diseases. In this study, we employed microarray and qRT-PCR to evaluate the potential circulating circRNAs with diagnostic efficacy in ovarian cancer. Methods We used microarray to explore the circRNA expression profile in ovarian cancer patients’ plasma and quantitative real-time (qRT)-PCR approach to assessing the candidate circRNA’s expression. Then the receiver operating characteristic (ROC) curve was employed to analyze the diagnostic values of candidate circRNAs. The diagnostic model circCOMBO was a combination of hsa_circ_0003972 and hsa_circ_0007288 built by binary logistic regression. Then bioinformatic tools were used to predict their potential mechanisms. Results Hsa_circ_0003972 and hsa_circ_0007288 were downregulated in ovarian cancer patients’ plasma, tissues, and cell lines, comparing with the controls. Hsa_circ_0003972 and hsa_circ_0007288 exhibited diagnostic values with the Area Under Curve (AUC) of 0.724 and 0.790, respectively. circCOMBO showed a better diagnostic utility (AUC: 0.781), while the combination of circCOMBO and carbohydrate antigen 125 (CA125) showed the highest diagnostic value (AUC: 0.923). Furthermore, the higher expression level of hsa_circ_0007288 in both plasma and ovarian cancer tissues was associated with lower lymph node metastasis potential in ovarian cancer. Conclusions Our results revealed that hsa_circ_0003972 and hsa_circ_0007288 may serve as novel circulating biomarkers for ovarian cancer diagnosis.

Breast cancer is one of the most common malignant tumors in women worldwide. Circular RNA (circRNA) is a class of structurally stable non-coding RNA with a covalently closed circular structure. In recent years, with the development of high-throughput RNA sequencing, many circRNAs have been discovered and have proven to be clinically significant in the development and progression of breast cancer. Importantly, several regulators of circRNA biogenesis have been discovered. Here, we systematically summarize recent progress regarding the network of regulation governing the biogenesis, degradation, and distribution of circRNAs, and we comprehensively analyze the functions, mechanisms, and clinical significance of circRNA in breast cancer.

Objective: Malnutrition has been reported to be related to adverse prognosis in acute ischemic stroke (AIS) patients. Unfortunately, traditional nutritional assessment tools usually increase the workload of neurologists, which makes them unfeasible in the daily clinic work. We aimed to elucidate the association between the prognostic nutritional index (PNI), an easily obtainable baseline nutritional marker, and 3-month outcomes in AIS patients receiving intravenous thrombolysis (IVT).Research methods and procedures: The present study retrospectively included 405 patients. PNI was calculated as 5*lymphocyte count (109 /L) + serum albumin concentration (g/L), and the good prognosis was defined as modified Rankin Scale score of 0–3. The relationship between PNI and clinical parameters was evaluated. The multiple logistic regression model was performed to find out independent predictors of the 3-month outcomes.Results: We found that the patients in the low PNI group had a higher frequency of anemia (12.9 vs. 2.3%, P < 0.001) and a higher level of the Controlling nutritional status (CONUT) score (P < 0.001). The relationship between PNI and nutrition-related factors, such as body mass index (r = 0.208, P = 0.001), age (r = −0.329, P < 0.001), total cholesterol (r = 0.268, P < 0.001) and hemoglobin concentration (r = 0.328, P < 0.001), was significant. Low PNI value (adjusted odds ratio: 2.250, confidence interval: 1.192–4.249, p = 0.012) stayed as an independent predictor for the poor outcome at three months, after adjustment for potential confounders.Conclusions: The PNI was independently associated with 3-month outcomes in AIS patients undergoing IVT. As an easily obtainable nutritional marker, PNI may be a useful nutritional assessment tool in the clinic work.

Background: The study was aimed at investigating the potential role of chronic lymphocytic thyroiditis (CLT) in papillary thyroid cancer (PTC) prognosis in distinct age groups, as well as the association between CLT and recurrence risk estimation.Methods: A total of 635 adult patients were retrospectively analyzed. On the basis of postoperative pathology examination, 188 patients were diagnosed with coexistent CLT and the remaining 447 were classified as non-CLT. Then the characteristics of CLT-coexisted patients and non-CLT ones were compared respectively when patients were aged ≥55 years or below. The association among postoperative clinicopathological features were also analyzed using multivariate regression. In addition, the prognostic value of several variables relating to high-risk recurrence were estimated within different age groups.Results: When divided in two age groups (55 years as the line), non-CLT group had a remarkable frequency of small size lesion (D max ≤1cm) compared with CLT-coexisted patients (54.6% to 43.0%, p =0.016). In addition, non-CLT patients tended to have intrathyroidal extension as opposed to those with coexistent CLT (20.2% to 28.2%, p =0.05). In multivariate analysis, CLT still significantly acted as an independent risk factor of greater lesion size (D min >1 cm) (OR=1.7, p =0.02) and mildly promoted gross extrathyroidal extension (ETE) (OR=1.4, p =0.06). However, associations didn't emerge in the characteristics mentioned above with CLT when patients were ≥55 years old. The prognostic value of CLT in high-risk recurrence was evident only in patients aged 35-44 years. (OR=2.4, 95%CI:1.2-5.4, p =0.02). Greater lesion size independently promoted gross ETE, no matter patients were aged above 55 years or not. Besides, its prognostic value of high-risk recurrence was significant throughout all age groups. Conclusion: These findings revealed that CLT coexistence might be the unfavorable factor of PTC prognosis in young and middle-aged (

With respect to the intriguing biocompatibility and the stealthy functions of poly(ethylene glycol) (PEG), PEGylated nanoparticulates have been intensively engineered for utilities as drug delivery vehicles. To advocate the targeted drug transportation, targeting ligands were strategically installed onto the surface of PEGylated nanoparticulates. The previous in vitro investigations revealed that the ligand-specified cell endocytosis of nanoparticulates was pronounced for the nanoparticulates with adequately high PEG crowdedness. The present study aims to explore insight into the impact of PEGylation degree on in vivo tumor-targeted accumulation activities of cRGD-installed nanoparticulates. The subsequent investigations verified the importance of the PEGylation crowdedness in pursuit of prolonged retention in the blood circulation post intravenous administration. Unprecedentedly, the PEGylation crowdedness was also identified as a crucial important parameter to pursue the tumor-targeted accumulation. A plausible reason is the elevated PEGylation crowdedness eliciting the restricted involvement in nonspecific protein adsorption of nanoparticulates in the biological milieu and consequently pronouncing the ligand-receptor-mediated binding for the nanoparticulates. Noteworthy was the distinctive performance of the class of the proposed systems once utilized for transportation of the mRNA payload to the tumors. The protein expression in the targeted tumors appeared to follow a clear PEGylation crowdedness dependence manner, where merely 2-fold PEGylation crowdedness led to remarkably 10-fold augmentation in protein expression in tumors. Hence, the results provided important information and implications for design of active-targeting PEGylated nanomaterials to fulfill the targeting strategies in systemic applications.

Tetraphenylene (TPE), characterized as a lipophilic and aggregation-induced-emissive fluorophore, was used to incorporate into an electrostatic self-assembled polyethylenimine-poly(ethylene glycol) (PEI-PEG)/plasmid DNA (pDNA) complexed micelle. The hydrophobic character of TPE appeared to drive a higher degree of condensation of the pDNA payload, which consequently resulted in not only strengthened colloidal stability of the constructed polyplex micelle but also improved biocompatibility by virtue of the elevated PEG crowdedness owing to the TPE-induced collapse of pDNA. These beneficial consequences potentially permitted a larger number of polyplex micelles to be internalized into the cells. PEG segments were designed to enable selective detachment from polyplex micelles in acidic milieu, e.g., the tumor microenvironment, and intracellular endosome compartment, based on the strategic arrangement of acid-responsive cleavable linkage between PEG and PEI. Upon PEG detachment, the exposure of cationic PEI/TPE polyplex was allowed to directly interact with the cell membrane, endosome membrane, and charged intracellular species, thus promoting cell internalization, endosome escape, and the release of the pDNA payload. Of note, this association of cationic PEI/TPE polyplex with the endosomal membrane could be further facilitated with the aid of lipophilic TPE, thereby eliciting pronounced destabilization potency to the endosome membrane and exerting an endosomal escape function. Eventually, the proposed system of these facile strategies, including responsive PEG detachment and functional TPE incorporation, was proven to provide efficient gene expression in the targeted tumors with an appreciable safety profile via systemic administration.

The high vulnerability of mRNA necessitates the manufacture of delivery vehicles to afford adequate protection in the biological milieu. Here, mRNA was complexed with a mixture of cRGD-poly(ethylene glycol) (PEG)-polylysine (PLys) (thiol) and poly(N-isopropylacrylamide) (PNIPAM)-PLys(thiol). The ionic complex core consisting of opposite-charged PLys and mRNA was crosslinked though redox-responsive disulfide linkage, thereby avoiding structural disassembly for exposure of mRNA to harsh biological environments. Furthermore, PNIPAM contributed to prolonged survival in systemic circulation by presenting a spatial barrier in impeding accessibility of nucleases, e.g., RNase, due to the thermo-responsive hydrophilic-hydrophobic transition behavior upon incubation at physiological temperature enabling translocation of PNIPAM from shell to intermediate barrier. Ultimately, the cRGD ligand attached to the formulation demonstrated improved tumor accumulation and potent gene expression, as manifested by virtue of facilitated cellular uptake and intracellular trafficking. These results indicate promise for the utility of mRNA as a therapeutic tool for disease treatment.

Nucleic acid-based therapy has emerged as a revolutionary methodology for treatment of the diseases related to protein dysfunction; however, lack of systemically applicable synthetic delivery systems limits its current usage in local applications, particularly for DNA-based therapy with regard to the poor bioavailability in the systemic administrations. To overcome this obstacle, we compiled multiple chemistry-based strategies into the manufacture of the gene delivery formulations to pursue improved tolerability of DNA to the enzymatic degradation in the biological milieu and prolonged retention in the systemic circulation. Here, we constructed a distinctive multilayered functional architecture: plasmid DNA (pDNA) was electrostatically complexed with cationic poly(lysine) (polyplex) as the interior pDNA reservoir, which was further cross-linked by redox-responsive disulfide cross-linking to minimize the occurrence of polyplex disassembly through exchange reaction with the biological charged components. Still, the pDNA reservoir was spatially protected by a sequential thermoresponsive poly(N-isopropylacrylamide) palisade as the intermediate barrier and a biocompatible hydrophilic poly(ethylene glycol) (PEG) shell with the aim of preventing the accessibility of the biological species, particularly the nuclease degradation to the pDNA payload. Subsequent investigations validated the utilities of these strategies in accomplishing prolonged blood retention. In an attempt to apply this method for tumor therapy, ligand cyclic (Arg-Gly-Asp) peptide was attached at the distal end of PEG, validating prompted tumor-targeted delivery and gene expression of the loaded antiangiogenic gene at the targeted tumor cells and accordingly exerting antiangiogenesis of the tumors for abrogation of tumor growth. Together with its excellent safe profile, the proposed formulation suggests potential utility as a practical gene delivery system for treatment of intractable diseases.

Layered metal phosphonate, zinc phenylphosphonate (PPZn) was synthesized and used as a model benign nucleating agent for poly(butylene adipate) (PBA) to manipulate the crystallization behavior, polymorphic crystalline structure and biodegradation of PBA. Upon incorporation of PPZn, the crystallization temperature (Tc) and crystallinity of PBA increased. Meanwhile, the crystallization rate and spherulite density of PBA increased in the presence of PPZn, indicating that PPZn has an effective nucleating effect for PBA. PPZn is favorable for the formation of the PBA α-modification. Furthermore, PPZn would speed up highly the phase transition of PBA from the β- to α-one. PPZn significantly suppressed the biodegradation of PBA. Mechanisms for nucleating, preferential formation of the α-modification, accelerated phase transition and decreased degradation rate of PBA in the presence of PPZn have also been proposed. It is considered that layered metal phosphonate material is a new type of benign filler for controlling the polymorphic crystalline structure and biodegradation rate of the polymer, which is expected to further modify the property of the polymer and might widen the applications of biodegradable materials in the environmental and biomedical fields.

A novel type of supramolecular nanoparticle (SNP) was self-assembled based on the balance of forces including attractive supramolecular host–guest interactions and repulsive electrostatic interactions between the host and the guest polymers. β-cyclodextrin (CD) grafted positively charged or neutral poly(glycerol methacrylate) (P+CD or PCD) and negatively charged CD-modified poly(acrylic acid) (PAA–CD) were synthesized respectively as the host polymers. While 4-tert-butylphenyl group (TBP) grafted positive poly(glycerol methacrylate) (P+TBP) was synthesized as the guest polymer to study the influence of electrostatics in the host–guest systems between CD and TBP. The resulting P+CD/P+TBP SNPs, possessing good stability, will provide a guide for the future construction of SNPs and promote the development of SNPs as carriers for biomedical applications such as drug delivery agents.

A facile poly(ethylene glycol) (PEG) detachment scheme was utilized to control the PEGylation degree of the polymeric micelles. The performance of cyclic Arg-Gly-Asp (cRGD) as a targeted moiety was studied on a class of polymeric micelles with various PEGylation degrees, revealing that the specific cRGD-mediated cell affinity, thus the cellular uptake and implicated privileges including the ligand-specified favorable intracellular trafficking and consequent favorable biofunctions, was prominent for the polymeric micelles with high PEGylation degree. These results endow important information and implications for the design and development of targeted nanomedicine, particularly the delivery of vulnerable biological compounds.

Electron photodetachment from the aromatic anion phenolate excited into the π-π* singlet excited state (S(1)) in aqueous solution is studied with ultrafast transient absorption spectroscopy with a time resolution of better than 50 fs. Broad-band transient absorption spectra from 300 to 690 nm are recorded. The transient bands are assigned to the solvated electron, the phenoxyl radical, and the phenolate S(1) excited state, and confirmation of these assignments is achieved using both KNO(3) as electron quencher and time-resolved fluorescence to measure singlet excited state dynamics. The phenolate fluorescence lifetime is found to be short (∼20 ps) in water, but the fast decay is only in part due to the electron ejection channel from S(1). Using global target analysis, two electron ejection channels are identified, and we propose that both vibrationally hot S(1) state and the relaxed S(1) state are direct precursors for the solvated electron. Therefore, electron ejection is found just to compete with picosecond time scale vibrational relaxation and electronic radiationless decay channels. This contrasts markedly with100 fs electron detachment processes for inorganic anions.

The spectroscopy and dynamics of a novel molecular architecture that mimics natural light harvesting have been characterized. The deployment of 9,9-dimethyl-2-fluorenyl (DMF) chromophores in atactic macrocyclic poly(9,9-dimethyl-2-vinylfluorene) is similar to that in the light harvesting antenna LH2 of the purple photosynthetic bacteria. A variety of spectroscopic probes are used to study the dynamics in these novel polymer systems. The number of chromophores is tuned from 12-142 identical chromophore units. Steady-state absorption and emission measurements, time-resolved fluorescence, and ultrafast transient absorption anisotropy techniques provide evidence for distinct differences in the photophysics of matching molecular weight linear and cyclic polymers and of the occurrence of energy transfer in these polymers. There is direct evidence of energy transfer in these macrocycles manifested in the depolarization decay components, which are characterized by two exponentials and are substantially faster than observed for reorientation of the free DMF chromophore. The time constants for the macrocycles are 700-900 fs and 7-8 ps and are size dependent; the biexponential decay arises from conformational and stereochemical disorder and can be well described by a master equation simulation assuming Förster incoherent hopping on model polymer structures. The results suggest energy hopping between adjacent chromophores on a 1 ps time scale. The pathway for energy migration is shown to be primarily between nearest neighbors along the cyclic backbone, but there is a considerable spread in the site-to-site hopping rates. Small cycles adopt a pseudoplanar ring type arrangement of the chromophore transition dipoles as observed in bacterial light harvesting antenna, and it is found that the linear polymers also show similar short-range planarity of transition dipoles. Overall, it is found that such small macrocyclic polymers possess excellent characteristics for light harvesting among identical chromophores and behave as a circular photonic wire.

Photodetachment is a general property of condensed-phase anions exposed to visible or ultraviolet light, but its mechanism has not been fully explored until recently. The combination of femtosecond pump-probe experiments in both bulk liquids and solvated clusters and quantum mechanical descriptions of the relevant excited states has provided new insight into the spectroscopy, energetics, and dynamics of the detachment process. We review detachment phenomena for the prototypical atomic systems, iodide in water and sodide in tetrahydrofuran, and these systems provide the relevant framework for molecular systems. The iodide system has been studied in gas-phase clusters as well as bulk solution. This article also contrasts mechanisms as a function of energy from purely charge-transfer-to-solvent detachment to regimes in which there is direct and indirect participation of the bulk conduction band.

The time-dependent survival probability for photoelectrons produced following resonant excitation of I− in its first charge-transfer-to-solvent (CTTS) band is determined by femtosecond pump–probe spectroscopy. The solvent effect on localization and recombination dynamics of the detached solvated electrons in various hydroxylic solvents (H2O, CH3OH, C2H5OH, C3H7OH, C4H9OH) is studied. The data are consistent with a caged geminate pair being formed in the CTTS photodetachment step. In all solvents, the geminate recombination of the detached electron can be modeled as competition between diffusive escape from an attractive short-range potential (∼3kBT) and reverse electron transfer to reform ground state iodide.

In concentrated solutions of NaClO4 and Na2SO4, the quantum yield for free electron generated by detachment from photoexcited anions (such as I-, OH-, ClO^4-, and [SO3]^2-) linearly decreases by 6-12% per 1 M ionic strength. In 9 M sodium perchlorate solution, this quantum yield decreases by roughly an order of magnitude. Ultrafast kinetic studies of 200 nm photon induced electron detachment from Br-, HO- and [SO3]^2- suggest that the prompt yield of thermalized electron does not change in these solutions; rather, the ionic strength effect originates in more efficient recombination of geminate pairs. Within the framework of the recently proposed mean force potential (MFP) model of charge separation dynamics in such photosystems, the observed changes are interpreted as an increase in the short-range attractive potential between the geminate partners. Association of sodium cation(s) with the electron and the parent anion is suggested as the most likely cause for the observed modification of the MFP. Electron thermalization kinetics suggest that the cation associated with the parent anion (by ion pairing and/or ionic atmosphere interaction) is passed to the detached electron in the course of the photoreaction. The precise atomic-level mechanism for the ionic strength effect is presently unclear; any further advance is likely to require the development of an adequate quantum molecular dynamics model.

The competition between geminate recombination of electrons with their parent radicals and electron scavenging with H+ is directly time resolved with ∼100 fs resolution at several acid concentrations. Electrons were produced from iodide photodetachment or two-photon ionization of H2O. With regards to those produced from iodide photodetachment, the separation between primary and secondary I:e− recombination is established using a full numerical solution to the diffusion equation. Electron ejection is found to be short range and a potential well of ∼3kbT depth stabilizing the solvent caged pair is required to yield a satisfactory fit to experiment. From time-resolved scavenging data up to 5 M HCl, it is shown that the electron can be scavenged both inside and outside the caged pair by H+ with nearly equal efficiency. The steady-state scavenging yield as a function of scavenger concentration is then predicted based on the determined time-dependent recombination function. Reassessment of several benchmark scavenging experiments from the 1960’s leads to the conclusion that the primary yield of electrons after excitation of iodide is near unity.

A wire-guided, gravity-driven jet apparatus is described that produces optically stable thin films of liquids flowing at rates suitable for high repetition rate spectroscopy. Unlike conventional free-flowing jets, the design works well for low viscosity solvents including water and aqueous solutions of proteins. The construction of the wire guide, jet nozzle, and flow system is described. A stable water film whose thickness can be varied from 6 to 100 μm is demonstrated that has been employed in resonance Raman and femtosecond transient absorption experiments.

We report the use of second-harmonic generation (SHG) microscopy in conjunction with circular dichroism (CD) to differentiate normal skin from that in the connective tissue disorder osteogenesis imperfecta (OI). Osteogenesis imperfecta results from mutations in the collagen triple helix, where the individual chains are defective, leading to abnormal folding, and ultimately, abnormal fibril/fiber organization. Second-harmonic-generation circular dichroism successfully differentiated normal human and OI skin tissues, whereas other SHG polarization schemes did not provide discrimination, suggesting this approach has high sensitivity for studying the difference in chirality in the mutated collagen. We further suggest that the method has clinical diagnostic value, as it could be performed with minimal invasion.

Concentration gradients of ECM proteins play active roles in many areas of cell biology including wound healing and metastasis. They may also form the basis of tissue engineering scaffolds, as these can direct cell adhesion and migration and promote new matrix synthesis. To better understand cell–matrix interactions on attractive gradients, we have used multiphoton excited (MPE) photochemistry to fabricate covalently linked micro-structured gradients from fibronectin (FN). The gradient design is comprised of a parallel series of individual linear gradients with overall dimensions of approximately 800 × 800 µm, where a linear dynamic range of nearly 10-fold in concentration was achieved. The adhesion dynamics of 3T3 fibroblasts were investigated, where the cell morphology and actin cytoskeleton became increasingly elongated and aligned with the direction of the gradient at increasing protein concentration. Moreover, the cell morphologies are distinct when adhered to regions of differing FN concentration but with similar topography. These results show that the fabrication approach allows investigating the roles of contact guidance and ECM cues on the cell–matrix interactions. We suggest this design overcomes some of the limitations with other fabrication methods, especially in terms of 3D patterning capabilities, and will serve as a new tool to study cell–matrix interactions.

Second-harmonic generation (SHG) microscopy has emerged as a powerful modality for imaging fibrillar collagen in a diverse range of tissues. Because of its underlying physical origin, it is highly sensitive to the collagen fibril/fiber structure, and, importantly, to changes that occur in diseases such as cancer, fibrosis and connective tissue disorders. We discuss how SHG can be used to obtain more structural information on the assembly of collagen in tissues than is possible by other microscopy techniques. We first provide an overview of the state of the art and the physical background of SHG microscopy, and then describe the optical modifications that need to be made to a laser-scanning microscope to enable the measurements. Crucial aspects for biomedical applications are the capabilities and limitations of the different experimental configurations. We estimate that the setup and calibration of the SHG instrument from its component parts will require 2-4 weeks, depending on the level of the user's experience.

Nonlinear optics are used to study human ovarian cancer. SHG imaging elucidates structural differences in normal and malignant tissues. Cell adhesion/migration dynamics are examined with ECM models fabricated by multiphoton excited photochemistry.

Charge-transfer-to-solvent (CTTS) reactions of hydroxide induced by 200 nm monophotonic or 337 nm and 389 nm biphotonic excitation of this anion in aqueous solution have been studied by means of pump-probe ultrafast laser spectroscopy. Transient absorption kinetics of the hydrated electron, eaq-, have been observed, from a few hundred femtoseconds out to 600 ps, and studied as function of hydroxide concentration and temperature. The geminate decay kinetics are bimodal, with a fast exponential component (ca. 13 ps) and a slower power "tail" due to the diffusional escape of the electrons. For the biphotonic excitation, the extrapolated fraction of escaped electrons is 1.8 times higher than for the monophotonic 200 nm excitation (31% vs. 17.5% at 25 oC, respectively), due to the broadening of the electron distribution. The biphotonic electron detachment is very inefficient; the corresponding absorption coefficient at 400 nm is < 4 cm TW-1 M-1 (assuming unity quantum efficiency for the photodetachment). For [OH-] between 10 mM and 10 M, almost no concentration dependence of the time profiles of solvated electron kinetics was observed. At higher temperature, the escape fraction of the electrons increases with a slope of 3x10-3 K-1 and the recombination and diffusion-controlled dissociation of the close pairs become faster. Activation energies of 8.3 and 22.3 kJ/mol for these two processes were obtained. The semianalytical theory of Shushin for diffusion controlled reactions in the central force field was used to model the geminate dynamics. The implications of these results for photoionization of water are discussed., 44 pages, 9 figures; supplement: 4 pages, 7 figures; to be submitted to J. Chem. Phys

Three-dimensional crystal structures for the light harvesting antenna complexes of photosynthetic bacteria have recently been resolved [1]. This has led to a more profound understanding of how nature harvests sunlight in an efficient fashion. The antenna complex (LH2) is highly symmetric and the deployment of chromophores is cyclic. It is therefore of interest whether this architecture is important for the very rapid and efficient energy transfer - excitation hopping times at room temperature of ~100 fs have been reported [2]. In our investigations, the ring-like structure of LH2 is mimicked by novel two-dimensional macrocyclic polymers, which have recently been synthesized [3]. Such poly-vinyl aromatic polymers can be prepared with 10 – 50 chromophore groups (here the chromophore is 9,9 dimethylfluorene) that are pendent to the polymer backbone. In this report, the steady state and time-resolved spectroscopic properties of the macrocyclic polymers are compared with their linear analogs.

Ovarian cancer is the deadliest gynecological cancer, which may arise in part due to the concurrent invasion and metastasis of high grade tumors. It is thus crucial to gain insight into the adhesion and migration mechanisms in vivo, as this may ultimately lead to new treatment/detection options. To explore this possibility, we have used multiphoton excited photochemistry (MPE) to synthesize models of the ovarian basal lamina consisting of crosslinked laminin nanofibers to quantify the adhesion/migration dynamics. The nanostructured laminin patterns permit the systematic comparison of total migration, directed migration, adhesion, and morphology of "normal" immortalized human ovarian epithelial cells (IOSE) and three lines of varying metastatic potential (OVCA433, SKOV-3.ip1, and HEY-1 cells). We find that the migration of all the cell lines is directed by the crosslinked fibers, and that the contact guidance enhances the total migration rates relative to monolayers. These rates increase with increasing metastatic potential, and the more invasive cells are less rigid and more weakly adhered to the nanofibers. The extent of directed migration also depends on the cell polarity and focal adhesion expression. For the invasive cells, these findings are similar to the integrin-independent ameboid-like migration seen for polar cells in collagen gels. Collectively, the results suggest that contact mediated migration as well as decreased adhesion may be operative in metastasis of ovarian cancer in vivo.

Novel spear-like In?O?N nanostructures have been synthesized on a Si substrate via a simple thermal evaporation process by ammoniating the In-containing reactants at 1100??C. All the In?O?N nanostructures contain a long, thin pole with a diameter ranging from 20 to 100?nm and a huge spear-like tip at the end. The structure and morphology, as well as the crystallinity and composition of the In?O?N nanospears, were characterized by a scanning electron microscope (SEM), a transmission electron microscope (TEM) and the attached energy dispersive system (EDS). TEM analysis confirmed the cubic structure of In?O?N nanospears. Room-temperature cathodoluminescence (CL) measurement indicated that the In?O?N nanospears have a broad and strong light emission centred at ~454?nm with an unobvious shoulder in the range of 500?600?nm.