Intramolecular locking and coumarin insertion: a stepwise approach for TADF design.

Three novel TADF (thermally activated delayed fluorescence) emitters based on the well-studied Qx-Ph-DMAC fluorophore are designed and synthesized. The photophysical properties of these materials are studied from a theoretical and experimental point of view, demonstrating the cumulative effects of multiple small modifications that combine to afford significantly improved TADF performance. First, an extra phenyl ring is added to the acceptor part of Qx-Ph-DMAC to increase the conjugation length, resulting in BQx-Ph-DMAC, which acts as an intermediate molecular structure. Next, an electron-deficient coumarin unit is incorporated to fortify the electron accepting ability, affording ChromPy-Ph-DMAC with red-shifted emission. Finally, the conjugated system is further enlarged by 'locking' the molecular structure, generating DBChromQx-DMAC with further red-shifted emission. The addition of the coumarin unit significantly impacts the charge-transfer excited state energy levels with little effect on the locally excited states, resulting in a decrease of the singlet-triplet energy gap. As a result, the two coumarin-based emitters show considerably improved TADF performance in 1 w/w% zeonex films when compared to the initial Qx-Ph-DMAC structure. 'Locking' the molecular structure further lowers the singlet-triplet energy gap, resulting in more efficient reverse intersystem crossing and increasing the contribution of TADF to the total emission.

Deletion of GARP on mouse regulatory T cells is not sufficient to inhibit the growth of transplanted tumors.

GARP is a transmembrane protein that presents latent TGF-ß1 on the surface of regulatory T cells (Tregs). Neutralizing anti-GARP monoclonal antibodies that prevent the release of active TGF-ß1, inhibit the immunosuppressive activity of human Tregs in vivo. In this study, we investigated the contribution of GARP on mouse Tregs to immunosuppression in experimental tumors. Unexpectedly, Foxp3 conditional garp knockout (KO) mice challenged orthotopically with GL261 tumor cells or subcutaneously with MC38 colon carcinoma cells did not show prolonged survival or delayed tumor growth. Also, the suppressive function of KO Tregs was similar to that of wild type Tregs in the T cell transfer model in allogeneic, immunodeficient mice. In conclusion, garp deletion in mouse Tregs is not sufficient to impair their immunosuppressive activity in vivo.

Estimating evapotranspiration and drought stress with ground-based thermal remote sensing in agriculture: a review.

As evaporation of water is an energy-demanding process, increasing evapotranspiration rates decrease the surface temperature (Ts) of leaves and plants. Based on this principle, ground-based thermal remote sensing has become one of the most important methods for estimating evapotranspiration and drought stress and for irrigation. This paper reviews its application in agriculture. The review consists of four parts. First, the basics of thermal remote sensing are briefly reviewed. Second, the theoretical relation between Ts and the sensible and latent heat flux is elaborated. A modelling approach was used to evaluate the effect of weather conditions and leaf or vegetation properties on leaf and canopy temperature. Ts increases with increasing air temperature and incoming radiation and with decreasing wind speed and relative humidity. At the leaf level, the leaf angle and leaf dimension have a large influence on Ts; at the vegetation level, Ts is strongly impacted by the roughness length; hence, by canopy height and structure. In the third part, an overview of the different ground-based thermal remote sensing techniques and approaches used to estimate drought stress or evapotranspiration in agriculture is provided. Among other methods, stress time, stress degree day, crop water stress index (CWSI), and stomatal conductance index are discussed. The theoretical models are used to evaluate the performance and sensitivity of the most important methods, corroborating the literature data. In the fourth and final part, a critical view on the future and remaining challenges of ground-based thermal remote sensing is presented.

Combined experimental-theoretical NMR study on 2,5-bis(5-aryl-3-hexylthiophen-2-yl)-thiazolo[5,4-d]thiazole derivatives for printable electronics.

Four 2,5-bis(5-aryl-3-hexylthiophen-2-yl)thiazolo[5,4-d]thiazole derivatives have been synthesized and thoroughly characterized. The extended aromatic core of the molecules was designed to enhance the charge transport characteristics, and solubilizing hexyl side chains were introduced on the thiophene subunits to enable possible integration of these semiconducting small molecules in printable electronics. Complete elucidation of the chemical structures by detailed one-dimensional/two-dimensional NMR spectroscopy is described, providing interesting input for chemical shift prediction software as well, because limited experimental data on these types of compounds are currently available. Furthermore, theoretical calculations have assisted experimental observations--giving support for the chemical shift assignment and providing a springboard for future screening and predictions--demonstrating the benefits of a coordinated theoretical-experimental approach.

Raising questions in clinical practice.

Answers are required by family physicians to numerous questions during a day of patient care. This study examined the number of questions that arose during one day to which family physicians did not have an answer, the library resources to which the family physicians had access and used, and the relationship between the number of questions that arose in practice and library resources or use. Volunteer family physicians (N = 87) reported a mean of 6.8 questions. When accessing libraries, physicians relied primarily on their office and home libraries. Personal libraries had fewer than ten textbooks published since 1980 and subscriptions to fewer than five journals. T-test analysis indicated that the physician with the most questions practiced in the medical school community, was a graduate of a Canadian or United States medical school, and attended a course on problem raising and solving. The number of questions did not differ by the holdings in the physician's library, the age or sex profile of the patients, the number of patients seen or the frequency with which the physician used his personal library. Medical educators and librarians should provide educational opportunities to assist family physicians develop their personal libraries, their problem solving skills and their use of modern technology to access the literature.

A medical information networking system between practitioners and academia.

This paper reports on a one-year experience with an information networking system (MIS) between 47 rural practitioners and an academic center. Physicians were invited to phone in non-emergency clinical questions specific to daily practice needs to a telephone answering service located in the medical school library. Two-hundred-forty questions triggered by patient visits, colleagues, local rounds, allied health or local professionals, and on-site administrative meetings were forwarded to the MIS. All inquiries were classified according to the International Classification of Disease-9th Revision-Clinical Modification, and categorized into three areas of practice: diagnostic/investigative, general treatment, and pharmacology (therapeutics). The paper outlines how specific practice questions are being screened and adopted for decisions relating to four current activities which assist the ongoing maintenance of competence: 1) CME program planning, 2) residency/undergraduate curriculum development, 3) individualized CME for specific practitioners and sites, and 4) future CME research. The physician inquiries represent true needs in rural medical practice and as such should be given high priority in programs and assessments addressing the maintenance of competence.

Functionalization of boron-doped nanocrystalline diamond with N3 dye molecules.

N3 dye molecules [cis-bis(isothiocyanato)bis(2,2'-bipyridyl-4,4'-dicarboxylato)ruthenium(II)] are covalently attached to boron-doped nanocrystalline diamond (B:NCD) thin films through a combination of coupling chemistries, i.e., diazonium, Suzuki, and EDC-NHS. X-ray and ultraviolet photoelectron spectroscopy and near-edge X-ray absorption fine structure spectroscopy are used to verify the covalent bonding of the dye on the B:NCD surface (compared to a hydrogen-terminated reference). The spectroscopic results confirm the presence of a dense N3 chromophore layer, and the positions of the frontier orbitals of the dye relative to the band edge of the B:NCD thin film are inferred as well. Proof-of-concept photoelectrochemical measurements show a strong increase in the photocurrent compared to non-dye-functionalized B:NCD films. This study opens up the possibility of applying N3-sensitized B:NCD thin films as hole conductors in dye-sensitized solar cells.

Fingerprints for structural defects in poly(thienylene vinylene) (PTV): a joint theoretical-experimental NMR study on model molecules.

In the field of plastic electronics, low band gap conjugated polymers like poly(thienylene vinylene) (PTV) and its derivatives are a promising class of materials that can be obtained with high molecular weight via the so-called dithiocarbamate precursor route. We have performed a joint experimental-theoretical study of the full NMR chemical shift assignment in a series of thiophene-based model compounds, which aims at (i) benchmarking the quantum-chemical calculations against experiments, (ii) identifying the signature of possible structural defects that can appear during the polymerization of PTV's, namely head-to-head and tail-to-tail defects, and (iii) defining a criterion regarding regioregularity.

Technical advancement in regulatory T cell isolation and characterization using CD127 expression in patients with malignant glioma treated with autologous dendritic cell vaccination.

We have successfully treated over two hundred high-grade glioma (HGG) patients with immunotherapy consisting of vaccination with autologous dendritic cells (DCs) loaded with autologous tumour lysate. It has been documented that regulatory T cells (Treg) can counteract anti-tumour immune responses. Therefore, monitoring of Treg in these patients is essential. Up till now, Treg have been characterized based on the expression of the transcription factor Foxp3. Here, we validated IL-7 receptor alpha subunit (CD127)dim expression as a marker for human Treg within HGG patients, as a less laborious assay for routine use in tumour vaccination trials. We noted a strong positive correlation between Foxp3 expression and CD127dim expression in CD4+CD25+ and CD4+ cells. The suppressive function of CD4+CD127dim cells was assessed in an allogeneic mixed lymphocyte reaction (MLR). We conclude that CD127 staining is a fast, well-suited and reproducible Treg monitoring tool in HGG patients treated with immunotherapy.

In vivo bioluminescence imaging in an experimental mouse model for dendritic cell based immunotherapy against malignant glioma.

The value of bioluminescence imaging (BLI) for experimental cancer models has become firmly established. We applied BLI to the GL261 glioma model in the context of dendritic cell (DC) immunotherapy. Initial validation revealed robust linear correlations between in vivo, ex vivo and in vitro luciferase activity measurements. Ex vivo BLI demonstrated midline crossing and leakage of tumor cells. Orthotopically challenged mice followed with BLI showed an initial adaptation phase, after which imaging data correlated linearly with stereologically determined tumor dimensions. Transition from healthy to moribund state corresponded with an increasing in vivo flux but the onset of neurological deficit was clearly delayed compared to the onset of in vivo flux increase. BLI was implemented in prophylactic immunotherapy and imaging data were prognostic for therapy outcome. Three distinct response patterns were detected. Our data underscore the feasibility of in vivo BLI in an experimental immunotherapeutic setting in the GL261 glioma model.

Responses to non-emergency questions in rural medicine: their usefulness to practice decisions.

This study reports the nature of non-emergency, day-to-day practice-related questions which arose in rural practice and were phoned in to a medical information system (MIS). The usefulness of these questions, and their responses, to clinical decision-making is outlined. Sixty-seven practitioners from 10 rural communities enrolled in the project. In response to each inquiry two or three articles were sent to the practitioner and to a consultant for validation. At the conclusion of the study the questions posed, and their responses, were examined. Forty-six per cent of the questions received were categorized as diagnostic; 30% as management; and 24% as therapeutic. Questions were classified using the ICD.9.CM. Those most frequently posed were in the nervous system/sense organs (13%), injury/poisoning (9%), and genito-urinary (9%) categories. Interviews with doctors and consultants were conducted to assess the usefulness of the service. Study findings suggest that an MIS can provide helpful information for improving daily aspects of clinical care, doctor-patient communication, administrative decision-making, and physician education. Practitioners, consultants, and medical librarians reported benefits from this service.

Practice-generated questions: a method of formulating true learning needs of family physicians.

The importance of identifying true learning needs prior to planning and conducting educational programs is well documented. In this study a collection of 579 clinical questions forwarded by 87 family physicians in southern Alberta was reviewed and analysed to determine if the questions would cluster and, therefore, be useful as sources for planning continuing medical education (CME) conferences and newsletters. The nature of submitted questions was also examined to determine if particular groups of physicians, as identified by socio-demographic characteristics, significanly differed by type of questions submitted. The study findings indicate that the questions generated by the clinical practices of family practitioners did cluster into meaningful categories, and did vary significantly by identified physician groups. Questions relating to the genito-urinary system; adverse drug effects, interactions and contraindications; and nervous system and sense organs were most frequently submitted. The nature of questions generated differed significantly by gender, size of practice setting, and year and place of medical graduation. When highly relevant and specific clinical questions, as contrasted with broadly expressed needs, serve as sources of identified learning needs for CME planners, the daily clinical problems faced by practitioners are better addressed. The learning needs identified by this approach provide an optimum framework for planned CME to influence physician behaviour or practice patterns.

Preparing doctors for tomorrow: information management as a theme in undergraduate medical education.

The evolving nature of medical knowledge and technology requires that the practitioners of tomorrow be able to develop practice management and computer skills in order to enhance quality patient care, ongoing education, and research. The paper describes how the discipline of medical informatics can be integrated into an undergraduate medical curriculum, not as a course or series of courses but as a repeated theme throughout the 3-year system-based curriculum. Recommendations specific to integrating medical informatics into an undergraduate curriculum are outlined with respect to: (1) content; (2) content organization; (3) management; and (4) evaluation. Six areas of information and computer management applications are discussed. These are computer-assisted learning, retrieving and organizing information from computerised databases, the application of medical informatics tools to the critical appraisal of literature and associated statistical software packages, hospital- and office-based information systems, and electronic communications. Medical education has a history of resistance to change. Reference to guidelines and experiences of others who have negotiated information management and medical informatics changes into medical school environments can therefore be helpful. It is in this context that this paper is presented.