Molecular and cellular correlates of human nerve regeneration: ADCYAP1/PACAP enhance nerve outgrowth

We only have a rudimentary understanding of the molecular and cellular determinants of nerve regeneration and neuropathic pain in humans. This cohort study uses the most common entrapment neuropathy (carpal tunnel syndrome) as a human model system to prospectively evaluate the cellular and molecular correlates of neural regeneration and its relationship with clinical recovery. In 60 patients undergoing carpal tunnel surgery [36 female, mean age 62.5 (standard deviation 12.2) years], we used quantitative sensory testing and nerve conduction studies to evaluate the function of large and small fibres before and 6 months after surgery. Clinical recovery was assessed with the global rating of change scale and Boston Carpal Tunnel Questionnaire. Twenty healthy participants provided normative data [14 female, mean age 58.0 (standard deviation 12.9) years]. At 6 months post-surgery, we noted significant recovery of median nerve neurophysiological parameters (P < 0.0001) and improvements in quantitative sensory testing measures of both small and large nerve fibre function (P < 0.002). Serial biopsies revealed a partial recovery of intraepidermal nerve fibre density [fibres/mm epidermis pre: 4.20 (2.83), post: 5.35 (3.34), P = 0.001], whose extent correlated with symptom improvement (r = 0.389, P = 0.001). In myelinated afferents, nodal length increased postoperatively [pre: 2.03 (0.82), post: 3.03 (1.23), P < 0.0001] suggesting that this is an adaptive phenomenon. Transcriptional profiling of the skin revealed 31 differentially expressed genes following decompression, with ADCYAP1 (encoding pituitary adenylate cyclase activating peptide, PACAP) being the most strongly upregulated (log2 fold-change 1.87, P = 0.0001) and its expression was associated with recovery of intraepidermal nerve fibres. We found that human induced pluripotent stem cell-derived sensory neurons expressed the receptor for PACAP and that this peptide could significantly enhance axon outgrowth in a dose-dependent manner in vitro [neurite length PACAP 1065.0 µm (285.5), vehicle 570.9 μm (181.8), P = 0.003]. In conclusion, carpal tunnel release is associated with significant cutaneous reinnervation, which correlates with the degree of functional improvement and is associated with a transcriptional programme relating to morphogenesis and inflammatory processes. The most highly dysregulated gene ADCYAP1 (encoding PACAP) was associated with reinnervation and, given that this peptide signals through G-protein coupled receptors, this signalling pathway provides an interesting therapeutic target for human sensory nerve regeneration

Emerging Energy Possibilities

This Thesis presents a thorough study of the electron transfer (ET) processes, both inter-molecular - between dyes for dye-sensitized solar cells (DSSCs), and intra-molecular - in porphyrin based electron donor-bridge-electron acceptor model systems. The focus has been on charge separation and subsequent re-combination in the femtosecond-nanosecond range in both systems. Studying these processes on nanocrystalline mesoporous films in rather heterogeneous systems for solar cell application is quite a challenge. Therefore, the knowledge gained by studying the same type of processes in designed model systems is in-valuable. To this end, ET has been verified and studied in a series of donor-bridge-acceptor (D-B-A) model systems using femtosecond transient absorption. The D-B-A series show photo-induced ET with exponential distance dependence via superexchange interactions. The attenuation factor of the ET rate, beta, was shown to be direction specific, which is in accordance with the McConnell model. A parallel study of the influence of the barrier height showed that the decrease in electronic coupling for the charge recombination (CR) reaction could be correlated to the impact of charge location. The importance of charge location was also used to explain the large differences in energy conversion efficiency found for two solar cell dyes with differently conjugated anchoring groups adsorbed on TiO2. The disparity in energy conversion efficiency for these two dyes was ascribed to the effect of differences in electron density on the binding oxygens, rather than efficiency variations in the injection process. An exponential distance dependence for CR was found also for dyes adsorbed on TiO2, with attenuation factors similar to those found for the D-B-A system. In addition, the hole transfer to and from NiO films was studied for two p-type dyes that had shown great differences in current generation. The CR was found to be slower for the dye with the strongest charge transfer character which was, surprisingly, the dye with the poorest solar cell performance. The reason for the meagre energy conversion efficiency of this dye was suggested to be a lack of driving force for regeneration by the redox couple

"Oprah" i den senmoderna offentliga sfären. En textanalys av "The Oprah Winfrey Show" och dess funktion i samhället

The intention of this thesis is to examine "The Oprah Winfrey Show" and its position and functions in the public sphere. Particularly interesting aspects are like the linking of private and public issues, the show's potential as a forum for debate and dissemination of knowledge, and what types of criticism the show has been subjected to. The methods used dealt with the textual aspects of the show. Semiotic analysis and conversation analysis were applied to five episodes and a search of literature was made. The thesis rests on theories concerning television studies and talk shows, in addition to theories on modernity and identity. Other studies of talk shows and of Oprah Winfrey and her show were also useful. The thesis shows that "The Oprah Winfrey Show" has great potential for encouraging the democratic process. The survival of the public sphere requires media to reach out to the masses, which this show does. It fulfils democracy's needs for education, and, and more importantly, it makes obvious the connection between public and private obvious to these masses. However, at the same time the show does not present enough different perspectives. Most expert opinions are portrayed as undisputed fact, and there are no real debates

Då omgivningens krav blir för stor för individens förmåga : En kvalitativ studie av Barn- och ungdomspsykiatrins synsätt på flickor med ADHD

Godkännandedatum 2013-11-12</p

Kan en mediehändelse förändra världssynen? En kvalitativ fallstudie av synen på rapporteringen kring orkanen Katrina och amerikanernas socioekonomiska status

Denna studie syftar till att utforska synen på rapporteringen kring orkanen Katrina, samt om den förändrat synen på USA och amerikanernas socioekonomiska status. Grunden är den uppmärksamhet fattiga fick i bevakningen. Metoden är kvalitativ intervju och målet är att uppnå analytisk generaliserbarhet. Viktiga teoretiska utgångspunkter är Lippmanns texter om världssyn och agenda-setting, där områden som framing och third-person effect är framträdande. Analysen visar att intervjupersonerna främst är positiva till hur bevakningen fungerat. Den kritik som funnits har bl. a. gällt en överdrivet personkoncentrerad rapportering samt brist på efterrapportering. Konstaterat är även att intervjupersonernas världssyn delvis grundar sig på nyhetsmediernas rapportering men att den inte automatiskt förändras av den. Antingen anser de ha fått sina uppfattningar bekräftade, eller aningen förändrade. Det fastställs att flera av intervjupersonerna tror att andra människor påverkas mer av rapporteringen än dem själva

Interplay between Barrier Width and Height in Electron Tunneling: Photoinduced Electron Transfer in Porphyrin-Based Donor-Bridge-Acceptor Systems

The rate of electron tunneling in mol. donor-bridge-acceptor (D-B-A) systems is detd. both by the tunneling barrier width and height, i.e., both by the distance between the donor and acceptor as well as by the energy gap between the donor and bridge moieties. These factors are therefore important to control when designing functional electron transfer systems, such as constructs for photovoltaics, artificial photosynthesis, and mol. scale electronics. The authors have studied a set of D-B-A systems in which the distance and the energy difference between the donor and bridge states (DEDB) are systematically varied. Zinc(II) and gold(III) porphyrins were chosen as electron donor and acceptor because of their suitable driving force for photoinduced electron transfer (-0.9 eV in butyronitrile) and well-characterized photophysics. The authors have previously shown, in accordance with the superexchange mechanism for electron transfer, that the electron transfer rate is proportional to the inverse of DEDB in zinc/gold porphyrin D-B-A systems with bridges of const. edge to edge distance (19.6 .ANG.) and varying DEDB (3900-17,600 cm-1). Here, the authors use the same donor and acceptor but the bridge is shortened or extended giving a set of oligo-p-phenyleneethynylene bridges (OPE) with four different edge to edge distances ranging from 12.7 to 33.4 .ANG.. These two sets of D-B-A systems-ZnP-RB-AuP+ and ZnP-nB-AuP+-have one bridge in common, and hence, for the first time both the distance and DEDB dependence of electron transfer can be studied simultaneously in a systematic way. [on SciFinder (R)

Distance and Driving Force Dependencies of Electron Injection and Recombination Dynamics in Organic Dye-Sensitized Solar Cells

A series of dyes based on a triphenylamine donor and a rhodanine acetic acid anchor/acceptor for solar cell application has been studied with regards to electron injection and recombination kinetics using femtosecond transient absorption. The series contains three dyes, with estd. electron transfer distances ranging from 17.2 to 11.0 Å, and which have shown significant differences in energy conversion efficiencies. The injection and recombination kinetics were studied in the near-IR region where electrons in the conduction band of the TiO2 are suggested to absorb. For all dyes, the injection rate is larger than (200 fs)-1 which implies a quant. injection efficiency. Surprisingly, the subsequent recombination reaction has a rate that increases with increasing linker length. On the other hand, this behavior is consistent with the concomitant decrease in driving force for this series of dyes. Moreover, the lifetimes show exponential distance dependence when cor. for driving force and reorganization energy, which indicates a superexchange interaction between the electrons in TiO2 and the radical cations of the dyes. A dependence on probe wavelength of the attenuation factor was found, giving a β value of 0.38 Å-1 at 940 nm and 0.49 Å-1 at 1040 nm. The difference is suggested to be due to the difference in electronic coupling between fully sepd. dye cations and injected electrons vs. geminate electron-hole pairs. Addn. of tert-butylpyridine, which from previous work is known to cause a substantial drop in the incident photon-to-current-efficiency values for the studied dyes, was found to decrease the amt. of long-lived electrons in the TiO2 without affecting the injection rate

Effect of Anchoring Group on Electron Injection and Recombination Dynamics in Organic Dye-Sensitized Solar Cells

In the field of dye-sensitized solar cells the no. of different sensitizing dyes is increasing rapidly. To produce low-cost dyes, much work is being directed toward synthesizing all-org., Ru-free dyes with high extinction coeffs. and broad absorption bands with large solar spectrum overlap. One of the best dyes, the polyene-diphenylaniline dye D5L2A1, has a rather blue absorption with an IPCE onset at ∼650 nm, but it still has an energy conversion efficiency of almost 6%. To increase the overlap with the solar spectrum, the cyanoacrylic acid anchoring group was changed to rhodanine-3-acetic acid in the complex D5L2A3. This gave an IPCE onset at ∼750 nm, but unfortunately, it also decreased the overall efficiency to a modest 1.7%. By femtosecond transient absorption, the electron injection into TiO2 for the 2 dyes are ultrafast and indistinguishable with the time resoln. (<200 fs). However, charge recombination is also ultrafast, with different fractions of a ∼500 fs component for the 2 dyes. Yet, the fraction of the faster decay component is larger for D5L2A3 than for D5L2A1. An interpretation of changing the anchoring group is presented. Probably a lack of electron d. on the binding oxygens of the D5L2A3 LUMO, due to the rhodanine group, promotes a higher probability for electron injection to short-lived surface trap states compared to the situation for the fully-conjugated D5L2A1