Ueber einige neue Verbindungen des Cadmiums

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Vibronic origin of long-lived coherence in an artificial molecular light harvester

Natural and artificial light harvesting processes have recently gained new interest. Signatures of long lasting coherence in spectroscopic signals of biological systems have been repeatedly observed, albeit their origin is a matter of ongoing debate, as it is unclear how the loss of coherence due to interaction with the noisy environments in such systems is averted. Here we report experimental and theoretical verification of coherent exciton-vibrational (vibronic) coupling as the origin of long-lasting coherence in an artificial light harvester, a molecular J-aggregate. In this macroscopically aligned tubular system, polarization controlled 2D spectroscopy delivers an uncongested and specific optical response as an ideal foundation for an in-depth theoretical description. We derive analytical expressions that show under which general conditions vibronic coupling leads to prolonged excited-state coherence

Distributing Reflexivity through Co-laborative Ethnography

In ethnographic research and analysis, reflexivity is vital to achieving constant coordination between field and concept work. However, it has been conceptualized predominantly as an ethnographer’s individual mental capacity. In this article, we draw on ten years of experience in conducting research together with partners from social psychiatry and mental health care across different research projects. We unfold three modes of achieving reflexivity co-laboratively: contrasting and discussing disciplinary concepts in interdisciplinary working groups and feedback workshops; joint data interpretation and writing; and participating in political agenda setting. Engaging these modes reveals reflexivity as a distributed process able to strengthen the ethnographer’s interpretative authority, and also able to constantly push the conceptual boundaries of the participating disciplines and professions.Heinrich Böll Stiftung https://doi.org/10.13039/100009379Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659Peer Reviewe

Organic sediment pulses impact rivers across multiple levels of ecological organization

Sedimentation is a pervasive environmental pressure affecting rivers globally. Headwaters draining catchments rich in organic soils (i.e. peat) are particularly vulnerable to enhanced sedimentation caused by land management and environmental change, yet many of the ecological consequences of peat deposition are poorly understood. We conducted a BACI experiment in two rivers draining blanket peatland in northern England to test the effect of sediment inputs on water quality, macroinvertebrate drift, macroinvertebrate community structure, and ecosystem metabolism. Sediment addition increased concentrations of dissolved organic carbon, total oxidised nitrogen and suspended sediment concentration in rivers, and intensified the total drift of macroinvertebrates particularly at night. By contrast the abundance and richness of benthic macroinvertebrates was unaffected, except for declines in Coleoptera abundance in one river. The gross primary production of both rivers was strongly suppressed as the benthos was smothered by sediment. Community respiration also declined, albeit by different extents in the two rivers. Our experiment revealed that short-term pulses of organic sediment in rivers can have broad effects on water quality and biota, from influences on the dispersal of individual organisms to the modification of ecosystem processes. Organic sediments therefore warrant further examination, to include longer observation periods and more sites. It is particularly important to clarify the extent to which impacts extend from peatland streams into larger rivers downstream. Such studies are necessary to inform global management efforts to restore the integrity of river ecosystems under a range of water and biodiversity policy mechanisms

Frequent and sex-biased deletion of SLX4IP by illegitimate V(D)J-mediated recombination in childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) accounts for ∼25% of pediatric malignancies. Of interest, the incidence of ALL is observed ∼20% higher in males relative to females. The mechanism behind the phenomenon of sex-specific differences is presently not understood. Employing genome-wide genetic aberration screening in 19 ALL samples, one of the most recurrent lesions identified was monoallelic deletion of the 5′ region of SLX4IP. We characterized this deletion by conventional molecular genetic techniques and analyzed its interrelationships with biological and clinical characteristics using specimens and data from 993 pediatric patients enrolled into trial AIEOP-BFM ALL 2000. Deletion of SLX4IP was detected in ∼30% of patients. Breakpoints within SLX4IP were defined to recurrent positions and revealed junctions with typical characteristics of illegitimate V(D)J-mediated recombination. In initial and validation analyses, SLX4IP deletions were significantly associated with male gender and ETV6/RUNX1-rearranged ALL (both overall P < 0.0001). For mechanistic validation, a second recurrent deletion affecting TAL1 and caused by the same molecular mechanism was analyzed in 1149 T-cell ALL patients. Validating a differential role by sex of illegitimate V(D)J-mediated recombination at the TAL1 locus, 128 out of 1149 T-cell ALL samples bore a deletion and males were significantly more often affected (P = 0.002). The repeatedly detected association of SLX4IP deletion with male sex and the extension of the sex bias to deletion of the TAL1 locus suggest that differential illegitimate V(D)J-mediated recombination events at specific loci may contribute to the consistent observation of higher incidence rates of childhood ALL in boys compared with girl

TCR-transgenic T cells and YB-1-based oncolytic virotherapy improve survival in a preclinical Ewing sarcoma xenograft mouse model

BackgroundEwing sarcoma (EwS) is an aggressive and highly metastatic bone and soft tissue tumor in pediatric patients and young adults. Cure rates are low when patients present with metastatic or relapsed disease. Therefore, innovative therapy approaches are urgently needed. Cellular- and oncolytic virus-based immunotherapies are on the rise for solid cancers.MethodsHere, we assess the combination of EwS tumor-associated antigen CHM1319-specific TCR-transgenic CD8+ T cells and the YB-1-driven (i.e. E1A13S-deleted) oncolytic adenovirus XVir-N-31 in vitro and in a xenograft mouse model for antitumor activity and immunostimulatory properties.ResultsIn vitro both approaches specifically kill EwS cell lines in a synergistic manner over controls. This effect was confirmed in vivo, with increased survival using the combination therapy. Further in vitro analyses of immunogenic cell death and antigen presentation confirmed immunostimulatory properties of virus-infected EwS tumor cells. As dendritic cell maturation was also increased by XVir-N-31, we observed superior proliferation of CHM1319-specific TCR-transgenic CD8+ T cells only in virus-tested conditions, emphasizing the superior immune-activating potential of XVir-N-31.ConclusionOur data prove synergistic antitumor effects in vitro and superior tumor control in a preclinical xenograft setting. Combination strategies of EwS-redirected T cells and YB-1-driven virotherapy are a highly promising immunotherapeutic approach for EwS and warrant further evaluation in a clinical setting

More mentoring needed? A cross-sectional study of mentoring programs for medical students in Germany

<p>Abstract</p> <p>Background</p> <p>Despite increasing recognition that mentoring is essential early in medical careers, little is known about the prevalence of mentoring programs for medical students. We conducted this study to survey all medical schools in Germany regarding the prevalence of mentoring programs for medical students as well as the characteristics, goals and effectiveness of these programs.</p> <p>Methods</p> <p>A definition of mentoring was established and program inclusion criteria were determined based on a review of the literature. The literature defined mentoring as a steady, long-lasting relationship designed to promote the mentee's overall development. We developed a questionnaire to assess key characteristics of mentoring programs: the advocated mentoring model, the number of participating mentees and mentors, funding and staff, and characteristics of mentees and mentors (e.g., level of training). In addition, the survey characterized the mentee-mentor relationship regarding the frequency of meetings, forms of communication, incentives for mentors, the mode of matching mentors and mentees, and results of program evaluations. Furthermore, participants were asked to characterize the aims of their programs. The questionnaire consisted of 34 questions total, in multiple-choice (17), numeric (7) and free-text (10) format. This questionnaire was sent to deans and medical education faculty in Germany between June and September 2009. For numeric answers, mean, median, and standard deviation were determined. For free-text items, responses were coded into categories using qualitative free text analysis.</p> <p>Results</p> <p>We received responses from all 36 medical schools in Germany. We found that 20 out of 36 medical schools in Germany offer 22 active mentoring programs with a median of 125 and a total of 5,843 medical students (6.9 - 7.4% of all German medical students) enrolled as mentees at the time of the survey. 14 out of 22 programs (63%) have been established within the last 2 years. Six programs (27%) offer mentoring in a one-on-one setting. 18 programs (82%) feature faculty physicians as mentors. Nine programs (41%) involve students as mentors in a peer-mentoring setting. The most commonly reported goals of the mentoring programs include: establishing the mentee's professional network (13 programs, 59%), enhancement of academic performance (11 programs, 50%) and counseling students in difficulties (10 programs, 45%).</p> <p>Conclusions</p> <p>Despite a clear upsurge of mentoring programs for German medical students over recent years, the overall availability of mentoring is still limited. The mentoring models and goals of the existing programs vary considerably. Outcome data from controlled studies are needed to compare the efficiency and effectiveness of different forms of mentoring for medical students.</p

Multi-Organ Expression Profiling Uncovers a Gene Module in Coronary Artery Disease Involving Transendothelial Migration of Leukocytes and LIM Domain Binding 2: The Stockholm Atherosclerosis Gene Expression (STAGE) Study

Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue) and atherosclerotic and unaffected arterial wall (n = 40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n = 49/48) and one visceral fat (n = 59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54) relating to carotid stenosis (P = 0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P<10−27and−30). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the expression of 13 TEML genes in Ldb2–deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and, together with LDB2, merits further attention in CAD research